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Sample records for activating antimicrobial pro-inflammatory

  1. WNT signaling in activated microglia is pro-inflammatory: WNT/β-catenin signaling in microglia

    OpenAIRE

    Halleskog, Carina; Mulder, Jan; Dahlström, Jenny; Mackie, Ken; Hortobágyi, Tibor; Tanila, Heikki; Puli, Lakshman Kumar; Färber, Katrin; Harkany, Tibor; Schulte, Gunnar

    2010-01-01

    Microglia activation is central to the neuroinflammation associated with neurological and neurodegenerative diseases, particularly since activated microglia are often a source of pro-inflammatory cytokines. Despite decades-long research, the molecular cascade of pro-inflammatory transformation of microglia in vivo remains largely elusive. Here, we report increased β–catenin expression, a central intracellular component of WNT signaling, in microglia undergoing a pro-inflammatory morphogenic t...

  2. Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages.

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    Snodgrass, Ryan G; Boß, Marcel; Zezina, Ekaterina; Weigert, Andreas; Dehne, Nathalie; Fleming, Ingrid; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Pro-inflammatory cytokines secreted by adipose tissue macrophages (ATMs) contribute to chronic low-grade inflammation and obesity-induced insulin resistance. Recent studies have shown that adipose tissue hypoxia promotes an inflammatory phenotype in ATMs. However, our understanding of how hypoxia modulates the response of ATMs to free fatty acids within obese adipose tissue is limited. We examined the effects of hypoxia (1% O2) on the pro-inflammatory responses of human monocyte-derived macrophages to the saturated fatty acid palmitate. Compared with normoxia, hypoxia significantly increased palmitate-induced mRNA expression and protein secretion of IL-6 and IL-1β. Although palmitate-induced endoplasmic reticulum stress and nuclear factor κB pathway activation were not enhanced by hypoxia, hypoxia increased the activation of JNK and p38 mitogen-activated protein kinase signaling in palmitate-treated cells. Inhibition of JNK blocked the hypoxic induction of pro-inflammatory cytokine expression, whereas knockdown of hypoxia-induced transcription factors HIF-1α and HIF-2α alone or in combination failed to reduce IL-6 and only modestly reduced IL-1β gene expression in palmitate-treated hypoxic macrophages. Enhanced pro-inflammatory cytokine production and JNK activity under hypoxia were prevented by inhibiting reactive oxygen species generation. In addition, silencing of dual-specificity phosphatase 16 increased normoxic levels of IL-6 and IL-1β and reduced the hypoxic potentiation in palmitate-treated macrophages. The secretome of hypoxic palmitate-treated macrophages promoted IL-6 and macrophage chemoattractant protein 1 expression in primary human adipocytes, which was sensitive to macrophage JNK inhibition. Our results reveal that the coexistence of hypoxia along with free fatty acids exacerbates macrophage-mediated inflammation. PMID:26578520

  3. Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium.

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    Sharma, Arpeeta; Yuen, Derek; Huet, Olivier; Pickering, Raelene; Stefanovic, Nada; Bernatchez, Pascal; de Haan, Judy B

    2016-04-01

    A critical early event in the pathogenesis of atherosclerosis is vascular inflammation leading to endothelial dysfunction (ED). Reactive oxygen species and inflammation are inextricably linked and declining antioxidant defense is implicated in ED. We have previously shown that Glutathione peroxidase-1 (GPx1) is a crucial antioxidant enzyme in the protection against diabetes-associated atherosclerosis. In this study we aimed to investigate mechanisms by which lack of GPx1 affects pro-inflammatory mediators in primary aortic endothelial cells (PAECs) isolated from GPx1 knockout (GPx1 KO) mice. Herein, we demonstrate that lack of GPx1 prolonged TNF-α induced phosphorylation of P38, ERK and JNK, all of which was reversed upon treatment with the GPx1 mimetic, ebselen. In addition, Akt phosphorylation was reduced in GPx1 KO PAECs, which correlated with decreased nitric oxide (NO) bioavailability as compared to WT PAECs. Furthermore, IκB degradation was prolonged in GPx1 KO PAECS suggesting an augmentation of NF-κB activity. In addition, the expression of vascular cell adhesion molecule (VCAM-1) was significantly increased in GPx1 KO PAECs and aortas. Static and dynamic flow adhesion assays showed significantly increased adhesion of fluorescently labeled leukocytes to GPx1 KO PAECS and aortas respectively, which were significantly reduced by ebselen treatment. Our results suggest that GPx1 plays a critical role in regulating pro-inflammatory pathways, including MAPK and NF-κB, and down-stream mediators such as VCAM-1, in vascular endothelial cells. Lack of GPx1, via effects on p-AKT also affects signaling to eNOS-derived NO. We speculate based on these results that declining antioxidant defenses as seen in cardiovascular diseases, by failing to regulate these pro-inflammatory pathways, facilitates an inflammatory and activated endothelium leading to ED and atherogenesis. PMID:26569096

  4. The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.

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    Maria Ruweka Fernando

    Full Text Available Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.

  5. The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.

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    Fernando, Maria Ruweka; Reyes, Jose Luis; Iannuzzi, Jordan; Leung, Gabriella; McKay, Derek Mark

    2014-01-01

    Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.

  6. Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.

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    Anding Liu

    Full Text Available High mobility group box 1 (HMGB1 is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion.Liver grafts were cold preserved for 24 h and flushed with saline in hourly intervals to collect the effluent. Liver grafts, cold-preserved for 6 h, were transplanted into syngeneic recipients to obtain serum and liver samples 24 h after initiation of reperfusion. Addition of the effluent to a macrophage culture induced the synthesis of tumor necrosis factor-alpha (TNF-α and interleukin (IL-6. The stimulatory activity of graft effluent was reduced after depletion of HMGB1 via immunoprecipitation. Oxidation of the effluent HMGB1 using H(2O(2 attenuated its stimulatory activity as well. Liver transplantation of cold preserved grafts caused HMGB1 translocation and release as determined by immunohistochemistry and ELISA-assay, respectively. Using Western blot with non-reducing conditions revealed the presence of oxidized HMGB1 in liver samples obtained after 12 h and in effluent samples after 16 h of cold preservation as well as in liver and serum samples obtained 24 h after reperfusion.These observations confirm that post-translational oxidation of HMGB1 attenuates its pro-inflammatory activity. Oxidation of HMGB1 as induced during prolonged ischemia and by reoxygenation during reperfusion in vivo might also attenuate its pro-inflammatory activity. Our findings also call for future studies to investigate the mechanism of the inhibitory effect of oxidized HMGB1 on the pro-inflammatory potential.

  7. Differential activation of JAK enzymes in rheumatoid arthritis and autoimmune disorders by pro-inflammatory cytokines: potential drug targets

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    Malemud, Charles

    2010-01-01

    Charles J MalemudArthritis Research Laboratory, Division of Rheumatic Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USAAbstract: Although several pro-inflammatory cytokines including interleukin-6 (IL-6), IL-7, IL-12/IL-23, IL-17, IL-2, interferon, and the anti-inflammatory cytokines, IL-4/IL-13, IL-10, and IL-22, all activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in autoimmune disorders, ...

  8. Tissue kallikrein mediates pro-inflammatory pathways and activation of protease-activated receptor-4 in proximal tubular epithelial cells.

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    Wai Han Yiu

    Full Text Available Tissue kallikrein (KLK1 expression is up-regulated in human diabetic kidney tissue and induced by high glucose (HG in human proximal tubular epithelial cells (PTEC. Since the kallikrein-kinin system (KKS has been linked to cellular inflammatory process in many diseases, it is likely that KLK1 expression may mediate the inflammatory process during the development of diabetic nephropathy. In this study, we explored the role of KLK1 in tubular pro-inflammatory responses under the diabetic milieu. Recombinant KLK1 stimulated the production of inflammatory cytokines in PTEC via the activation of p42/44 and p38 MAPK signaling pathways. Molecular knockdown of endogenous KLK1 expression by siRNA transfection in PTEC attenuated advanced glycation end-products (AGE-induced IL-8 and ICAM-1 productions in vitro. Interestingly, exposure of PTEC to KLK1 induced the expression of protease-activated receptors (PARs. There was a 2.9-fold increase in PAR-4, 1.4-fold increase in PAR-1 and 1.2-fold increase in PAR-2 mRNA levels. Activation of PAR-4 by a selective agonist was found to elicit the pro-inflammatory and pro-fibrotic phenotypes in PTEC while blockade of the receptor by specific antagonist attenuated high glucose-induced IL-6, CCL-2, CTGF and collagen IV expression. Calcium mobilization by the PAR-4 agonist in PTEC was desensitized by pretreatment with KLK1. Consistent with these in vitro findings, there was a markedly up-regulation of tubular PAR-4 expression in human diabetic renal cortical tissues. Together, these results suggest that up-regulation of KLK1 in tubular epithelial cells may mediate pro-inflammatory pathway and PAR activation during diabetic nephropathy and provide a new therapeutic target for further investigation.

  9. Tissue kallikrein mediates pro-inflammatory pathways and activation of protease-activated receptor-4 in proximal tubular epithelial cells.

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    Yiu, Wai Han; Wong, Dickson W L; Chan, Loretta Y Y; Leung, Joseph C K; Chan, Kwok Wah; Lan, Hui Yao; Lai, Kar Neng; Tang, Sydney C W

    2014-01-01

    Tissue kallikrein (KLK1) expression is up-regulated in human diabetic kidney tissue and induced by high glucose (HG) in human proximal tubular epithelial cells (PTEC). Since the kallikrein-kinin system (KKS) has been linked to cellular inflammatory process in many diseases, it is likely that KLK1 expression may mediate the inflammatory process during the development of diabetic nephropathy. In this study, we explored the role of KLK1 in tubular pro-inflammatory responses under the diabetic milieu. Recombinant KLK1 stimulated the production of inflammatory cytokines in PTEC via the activation of p42/44 and p38 MAPK signaling pathways. Molecular knockdown of endogenous KLK1 expression by siRNA transfection in PTEC attenuated advanced glycation end-products (AGE)-induced IL-8 and ICAM-1 productions in vitro. Interestingly, exposure of PTEC to KLK1 induced the expression of protease-activated receptors (PARs). There was a 2.9-fold increase in PAR-4, 1.4-fold increase in PAR-1 and 1.2-fold increase in PAR-2 mRNA levels. Activation of PAR-4 by a selective agonist was found to elicit the pro-inflammatory and pro-fibrotic phenotypes in PTEC while blockade of the receptor by specific antagonist attenuated high glucose-induced IL-6, CCL-2, CTGF and collagen IV expression. Calcium mobilization by the PAR-4 agonist in PTEC was desensitized by pretreatment with KLK1. Consistent with these in vitro findings, there was a markedly up-regulation of tubular PAR-4 expression in human diabetic renal cortical tissues. Together, these results suggest that up-regulation of KLK1 in tubular epithelial cells may mediate pro-inflammatory pathway and PAR activation during diabetic nephropathy and provide a new therapeutic target for further investigation. PMID:24586431

  10. Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells

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    Jane T. Jones

    2016-08-01

    Full Text Available Nuclear Factor kappa B (NF-κB is a transcription factor family critical in the activation of pro- inflammatory responses. The NF-κB pathway is regulated by oxidant-induced post-translational modifications. Protein S-glutathionylation, or the conjugation of the antioxidant molecule, glutathione to reactive cysteines inhibits the activity of inhibitory kappa B kinase beta (IKKβ, among other NF-κB proteins. Glutathione S-transferase Pi (GSTP is an enzyme that has been shown to catalyze protein S-glutathionylation (PSSG under conditions of oxidative stress. The objective of the present study was to determine whether GSTP regulates NF-κB signaling, S-glutathionylation of IKK, and subsequent pro-inflammatory signaling. We demonstrated that, in unstimulated cells, GSTP associated with the inhibitor of NF-κB, IκBα. However, exposure to LPS resulted in a rapid loss of association between IκBα and GSTP, and instead led to a protracted association between IKKβ and GSTP. LPS exposure also led to increases in the S-glutathionylation of IKKβ. SiRNA-mediated knockdown of GSTP decreased IKKβ-SSG, and enhanced NF-κB nuclear translocation, transcriptional activity, and pro-inflammatory cytokine production in response to lipopolysaccharide (LPS. TLK117, an isotype-selective inhibitor of GSTP, also enhanced LPS-induced NF-κB transcriptional activity and pro-inflammatory cytokine production, suggesting that the catalytic activity of GSTP is important in repressing NF-κB activation. Expression of both wild-type and catalytically-inactive Y7F mutant GSTP significantly attenuated LPS- or IKKβ-induced production of GM-CSF. These studies indicate a complex role for GSTP in modulating NF-κB, which may involve S-glutathionylation of IKK proteins, and interaction with NF-κB family members. Our findings suggest that targeting GSTP is a potential avenue for regulating the activity of this prominent pro-inflammatory and immunomodulatory transcription factor.

  11. Beta-defensins activate macrophages and synergize in pro-inflammatory cytokine expression induced by TLR ligands.

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    Barabas, Nicola; Röhrl, Johann; Holler, Ernst; Hehlgans, Thomas

    2013-07-01

    Our previous studies indicated that mouse beta defensin 14 (mBD14, Defb14), a newly identified member of the beta-defensin super family, interacts with the chemokine receptors CCR2 and CCR6. In this study we report that pre-stimulation of primary mouse macrophages with mBD14 results in a synergistic, enhanced expression of pro-inflammatory cytokines and chemokines induced by TLR ligand re-stimulation. Experiments using specific inhibitors of G(i)-protein-coupled receptor signaling provide evidence that this effect seems to be mediated by a G(i)-protein-coupled receptor expressed on bone marrow derived macrophages. However, using primary macrophages derived from CCR6- and CCR2-deficient mice clearly demonstrated that the enhanced pro-inflammatory cytokine and chemokine expression is independent of the chemokine receptors CCR6 and CCR2. Additionally, signaling pathway analysis indicated that mBD14 is capable of inducing MAPK ERK1/2 phosphorylation and the induction of CD86 and F4/80 expression in bone marrow-derived macrophages after mBD14 stimulation. Collectively, our data indicate that β-defensins activate primary macrophages and enhance pro-inflammatory responses by using G(i)PCRs in order to support inflammatory reactions induced by TLR ligands. PMID:23332217

  12. Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

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    Somenath Banerjee; Dipayan Bose; Nabanita Chatterjee; Subhadip Das; Sreeparna Chakraborty; Tanya Das; Krishna Das Saha

    2016-01-01

    Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these...

  13. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

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    Chakravarthy, Harshini; Beli, Eleni; Navitskaya, Svetlana; O'Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B; Busik, Julia V

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  14. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

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    Harshini Chakravarthy

    Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  15. Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes.

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    Norström, Melissa M; Rådestad, Emelie; Sundberg, Berit; Mattsson, Jonas; Henningsohn, Lars; Levitsky, Victor; Uhlin, Michael

    2016-04-26

    Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer. PMID:26993768

  16. Mechanism of the pro-inflammatory activity of sympathomimetic amines in thermic oedema of the rat paw.

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    Green, K L

    1974-02-01

    1 Thermic oedema induced by heating rat paws at 46.5 degrees C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro-inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.2 The subcutaneous space of heated rat paws was perfused with Tyrode solution and the perfusate collected and assayed for bradykinin, bradykininogen, kinin-forming activity and kininase activity. When adrenaline (0.5 mug/ml) was included in the perfusion fluid, kininase activity of the perfusate was increased by 76% and free bradykinin reduced by 46%.3 Increased vascular permeability induced by injection of bradykinin or kallikrein was reduced by adrenaline or noradrenaline, but isoprenaline had no significant effect.4 Pretreatment with soya bean trypsin inhibitor (SBTI) or heparin did not antagonize the pro-inflammatory effect of adrenaline or thermic oedema per se.5 Potentiation of thermic oedema similar to that induced by sympathomimetic amines was obtained by injecting paws with vasopressin prior to heating, or by applying a ligature to stop blood flow to the paw for the first 15 min of heating.6 Thermistor probes inserted beneath the paw skin showed that sympathomimetic amines increased the internal temperature of heated paws. This was significant, as small changes in temperature had a marked effect on the development of thermic oedema.7 It is suggested that sympathomimetic amines potentiate thermic oedema of rat paws heated at 46.5 degrees C by reducing blood flow to the paw, thereby causing a greater rise in paw temperature and consequently greater injury. PMID:4371900

  17. Sintered indium-tin oxide particles induce pro-inflammatory responses in vitro, in part through inflammasome activation.

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    Melissa A Badding

    Full Text Available Indium-tin oxide (ITO is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO, and ventilation dust particles activated nuclear factor kappa B (NFκB within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1β, IL-6, TNFα, and IL-8 within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1β release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue.

  18. Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

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    David A White

    Full Text Available OBJECTIVES: Macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI. METHODS AND RESULTS: We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9 and interleukin-6 (IL-6 in cultured peripheral blood mononuclear cells (PBMCs and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1β which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI. CONCLUSION: MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests

  19. Macrophage colony-stimulating factor (CSF-1) induces pro-inflammatory gene expression and enhances antimicrobial responses of goldfish (Carassius auratus L.) macrophages.

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    Grayfer, Leon; Hanington, Patrick C; Belosevic, Miodrag

    2009-03-01

    We report on the regulation of pro-inflammatory functions of goldfish macrophages and induction of gene expression by recombinant goldfish CSF-1 (rgCSF-1). Recombinant goldfish TNFalpha-2 (rg TNFalpha-2), rgIFNgamma but not rgTGFbeta induced time-dependent increase of CSF-1 expression in macrophages. Treatment of goldfish macrophages with rgCSF-1 increased expression of several immune genes including CXCL-8 (=IL-8), CCL-1, TNFalpha-1, TNFalpha-2, IL-1beta-1, IL-1beta-2, IL-12-p35, IL-12-p40, IFN, IL-10 and iNOS A and B. The rgCSF-1 treatment did not significantly alter the mRNA levels of TGFbeta and NRAMP in macrophages up to 48h post treatment. However, at 72h post treatment, the expression of TGFbeta increased whereas that of NRAMP decreased. The treatment of macrophages with rgCSF-1 enhanced their respiratory burst and nitric oxide responses that were abrogated after addition of soluble CSF-1 receptor (sCSF-1R) to cell cultures. Macrophages exhibited a concentration-dependent chemotactic response toward rgCSF-1 as well as an increase in phagocytic activity that was abrogated after addition of sCSF-1R to cell cultures. Our results indicate that in addition to being an important growth factor of goldfish macrophages, rgCSF-1 also plays a central role in the regulation of their pro-inflammatory responses. PMID:19130890

  20. Cardiac Glycosides Inhibit LPS-induced Activation of Pro-inflammatory Cytokines in Whole Blood through an NF-kappa-B-dependent Mechanism

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    Shah VO*

    2011-03-01

    Full Text Available Summary: The process of hemodialysis (HD produces a pro-inflammatory state that can lead to an increased risk for cardiovascular disease. In part, this is the result of activation of the pro-inflammatory transcription factor NF-B in response to uremia as well as in response to HD itself, which not only involves exposure of blood leukocytes to abnormal surfaces but also potentially to any bacterial contamination associated with HD. Previously, we used lipopolysaccharide (LPS to activate isolated peripheral blood mononuclear cells (PBMC, as a model of HD-induced stress, and demonstrated that specific natural products that are known to inhibit the activation of NF-B exhibited a broad anti-inflammatory activity. These natural products, however, were not effective when whole blood was used. In the present study, a natural product library (TimTec NPL480 was screened, using whole blood, for the abilities of these natural products to protect against LPS-induced expression and secretion of the pro-inflammatory cytokines TNF, IL-1 and IL-6. We report here that the cardiac glycosides strophanthidin, ouabain, proscillaridin A, digoxin, digitoxin and lanatoside C are effective natural products that limit the development of a pro-inflammatory state by preventing the activation of these pro-inflammatory signals. These active natural products also inhibited the stress-induced activation of NF-B in a reporter assay, suggesting that inhibition of NF-kappa-B is at least partly the mechanism by which these natural products protect whole blood leukocytes from activation by LPS. Industrial relevance: Media for hemodialysis is used millions of times annually for patients with end stage renal disease, each use representing a potential pro-inflammatory insult. It would be useful to have a drug that could be added to the media which would protect blood leukocytes from any pro-inflammatory activation that may accompany the dialysis procedure. A natural

  1. PGH1, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP2

    DEFF Research Database (Denmark)

    Schröder, Ralf; Xue, Luzheng; Konya, Viktoria;

    2012-01-01

    Prostaglandin H(1) (PGH(1)) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as "anti-inflammatory". Herein we present evidence that PGH(1) is a potent activator of the pro-inflammatory PGD(2) receptor ...

  2. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

    Science.gov (United States)

    Ip, Margaret; Chu, Yi Jun; Yung, Irene M. H.; Cheung, Catherine S. K.; Zheng, Lin; Lam, Judy S. Y.; Wong, Ka Tak; Sin, Winnie W. Y.; Choi, Kin Wing; Lee, Nelson

    2016-01-01

    Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, PCXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. Conclusion In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control. PMID:27434276

  3. Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.

    Science.gov (United States)

    Mon, Htwe H; Christo, Susan N; Ndi, Chi P; Jasieniak, Marek; Rickard, Heather; Hayball, John D; Griesser, Hans J; Semple, Susan J

    2015-12-24

    The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management. PMID:26636180

  4. Analysis of the physical activity effects and measurement of pro-inflammatory cytokines in irradiated lungs in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Renata Cristiane Gennari; Katashima, Carlos Kiyoshi [Faculty of Medical Sciences, UNICAMP, Campinas, SP (Brazil); Ropelle, Eduardo Rochete [School of Applied Sciences, University of Campinas, UNICAMP, Limeira, SP (Brazil); Carvalheira, Jose Barreto Campello [Department of Internal Medicine, UNICAMP, Campinas, SP (Brazil); Lopes, Luiz Roberto; Andreollo, Nelson Adami [Department of Surgery, UNICAMP, Campinas, SP (Brazil)

    2012-03-15

    Purpose: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -{beta} (tgf -{beta}), tumor necrosis factor -a (tnf-a) and protein beta kinase {beta} (ikk{beta}), through western blotting analysis. Methods: A randomized study with 28 Wistar Hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. Results: The cytokines IKK{beta}, TNF-{alpha} and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-{beta}. Conclusion: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise preradiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation. (author)

  5. Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells.

    Science.gov (United States)

    Prabhala, Pavan; Bunge, Kristin; Ge, Qi; Ammit, Alaina J

    2016-10-01

    Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroids. MKP-1 is known to deactivate p38 MAPK phosphorylation and can control the expression and activity of the mRNA destabilizing protein-tristetraprolin (TTP). But whether corticosteroid-induced MKP-1 acts via p38 MAPK-mediated modulation of TTP function in a pivotal airway cell type, airway smooth muscle (ASM), was unknown. While pretreatment of ASM cells with the corticosteroid dexamethasone (preventative protocol) is known to reduce ASM synthetic function in vitro, the impact of adding dexamethasone after stimulation (therapeutic protocol) had not been explored. Whether dexamethasone modulates TTP in a p38 MAPK-dependent manner in this cell type was also unknown. We address this herein and utilize an in vitro model of asthmatic inflammation where ASM cells were stimulated with the pro-asthmatic cytokine tumor necrosis factor (TNF) and the impact of adding dexamethasone 1 h after stimulation assessed. IL-6 mRNA expression and protein secretion was significantly repressed by dexamethasone acting in a temporally distinct manner to increase MKP-1, deactivate p38 MAPK, and modulate TTP phosphorylation status. In this way, dexamethasone-induced MKP-1 acts via p38 MAPK to switch on the mRNA destabilizing function of TTP to repress pro-inflammatory cytokine secretion from ASM cells. J. Cell. Physiol. 231: 2153-2158, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825339

  6. Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

    Directory of Open Access Journals (Sweden)

    M Mojtahedzadeh

    2011-05-01

    Full Text Available "n  "n Background and the purpose of the study: Besides its hematopoietic effects, erythropoietin (EPO by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. "n Methods: Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO (received EPO, 300 units/Kg/day and Control (not received EPO groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha (TNF-α, Interleukin 1 (IL-1, Plasminogen Activator Inhibitor 1 (PAI-1 and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA scores were also recorded. "n Results: Among 12 patients (EPO group TNF-α level at the day of 9 (P=0.046, and within EPO group at the days of 3 (P=0.026 ameliorate, 6 (P=0.016, and 9 (P=0.052 were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals (the first, third and seventh days. "n Conclusion: From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma.

  7. Deletion of caspase-8 in mouse myeloid cells blocks microglia pro-inflammatory activation and confers protection in MPTP neurodegeneration model.

    Science.gov (United States)

    Kavanagh, Edel; Burguillos, Miguel Angel; Carrillo-Jimenez, Alejandro; Oliva-Martin, María José; Santiago, Martiniano; Rodhe, Johanna; Joseph, Bertrand; Venero, Jose Luis

    2015-09-01

    Increasing evidence involves sustained pro-inflammatory microglia activation in the pathogenesis of different neurodegenerative diseases, particularly Parkinson's disease (PD). We recently uncovered a completely novel and unexpected role for caspase-8 and its downstream substrates caspase-3/7 in the control of microglia activation and associated neurotoxicity to dopaminergic cells. To demonstrate the genetic evidence, mice bearing a floxed allele ofCASP8 were crossed onto a transgenic line expressing Cre under the control of Lysozyme 2 gene. Analysis of caspase-8 gene deletion in brain microglia demonstrated a high efficiency in activated but not in resident microglia. Mice were challenged with lipopolysaccharide, a potent inducer of microglia activation, or with MPTP, which promotes specific dopaminergic cell damage and consequent reactive microgliosis. In neither of these models, CASP8 deletion appeared to affect the overall number of microglia expressing the pan specific microglia marker, Iba1. In contrast, CD16/CD32 expression, a microglial pro-inflammatory marker, was found to be negatively affected upon CASP8 deletion. Expression of additional proinflammatory markers were also found to be reduced in response to lipopolysaccharide. Of importance, reduced pro-inflammatory microglia activation was accompanied by a significant protection of the nigro-striatal dopaminergic system in the MPTP mouse model of PD.

  8. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  9. Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro-inflammatory cytokines in human dendritic cells challenged with Salmonella typhi through TLR activation.

    Directory of Open Access Journals (Sweden)

    Miriam Bermudez-Brito

    Full Text Available Dendritic cells (DCs constitute the first point of contact between gut commensals and our immune system. Despite growing evidence of the immunomodulatory effects of probiotics, the interactions between the cells of the intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of this work was to determine whether the probiotic Bifidobacterium breve CNCM I-4035 and its cell-free culture supernatant (CFS have immunomodulatory effects in human intestinal-like dendritic cells (DCs and how they respond to the pathogenic bacterium Salmonella enterica serovar Typhi, and also to elucidate the molecular mechanisms involved in these interactions. Human DCs were directly challenged with B. breve/CFS, S. typhi or a combination of these stimuli for 4 h. The expression pattern of genes involved in Toll-like receptor (TLR signaling pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with S. typhi. In contrast, the B. breve CNCM I-4035 probiotic strain was a potent inducer of the pro-inflammatory cytokines and chemokines tested, i.e., TNF-α, IL-8 and RANTES, as well as anti-inflammatory cytokines including IL-10. CFS restored TGF-β levels in the presence of Salmonella. Live B.breve and its supernatant enhanced innate immune responses by the activation of TLR signaling pathway. These treatments upregulated TLR9 gene transcription. In addition, CFS was a more potent inducer of TLR9 expression than the probiotic bacteria in the presence of S. typhi. Expression levels of CASP8 and IRAK4 were also increased by CFS, and both treatments induced TOLLIP gene expression. Our results indicate that the probiotic strain B. breve CNCM I-4035 affects the intestinal immune response, whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This supernatant may protect immune system from highly infectious agents such as Salmonella typhi and can down

  10. The inhibitory activity of cocoa phenolic extract against pro-inflammatory mediators secretion induced by lipopolysaccharide in RAW 264.7 cells.

    Science.gov (United States)

    Ranneh, Yazan; Ali, Faisal; Al-Qubaisi, Mothanna; Esa, Norhaizan Mohd; Ismail, Amin

    2016-01-01

    Cocoa is a rich source of polyphenols that has been traditionally used as the treatment of several types of inflammation related disease. The response to inflammation comprises the consecutive release of mediators and the enlistment of circulating leukocytes, such as macrophages. Currently, Cocoa-derived polyphenolics have shown anti-inflammatory effects in vivo, but the therapeutic benefits in vitro remain unclear. Therefore, in this study, the effect of cocoa polyphenolic extract (CPE) on RAW 264.7 macrophage cells sensitized by lipopolysaccharide as in vitro inflammatory model was investigated. The anti-inflammatory activity of CPE was assessed by measuring its ability to inhibit the pro-inflammatory enzyme 5-lipoxygenase (5-LOX) and the pro-inflammatory mediators prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). The results show that CPE significantly inhibits 5-LOX activity (p < 0.01). In addition, CPE dose-dependently suppressed the production of PGE2, ROS, NO and TNF-α in RAW 264.7 cells. These data suggest that CPE may be used for the treatment of inflammation and it's related-diseases. PMID:27190746

  11. Expression of T-cell KV1.3 potassium channel correlates with pro-inflammatory cytokines and disease activity in ulcerative colitis

    DEFF Research Database (Denmark)

    Koch Hansen, Lars; Møller, Linda Maria Sevelsted; Rabjerg, Maj;

    2014-01-01

    BACKGROUND AND AIMS: Potassium channels, KV1.3 and KCa3.1, have been suggested to control T-cell activation, proliferation, and cytokine production and may thus constitute targets for anti-inflammatory therapy. Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized...... with active UC (n=33) and controls (n=15). Protein and mRNA expression of KV1.3 and KCa3.1, immune cell markers, and pro-inflammatory cytokines were determined by quantitative-real-time-polymerase-chain-reaction (qPCR) and immunofluorescence, and correlated with clinical parameters of inflammation. In......% of CD8(+) T-cells. KV1.3 was virtually absent on infiltrating macrophages. KV1.3 mRNA expression correlated significantly with mRNA expression of pro-inflammatory cytokines TNF-α (R(2)=0.61) and IL-17A (R(2)=0.51), the mayo endoscopic subscore (R(2)=0.13), and histological inflammation (R(2)=0.23). In...

  12. Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages.

    Science.gov (United States)

    Banerjee, Somenath; Bose, Dipayan; Chatterjee, Nabanita; Das, Subhadip; Chakraborty, Sreeparna; Das, Tanya; Saha, Krishna Das

    2016-01-01

    Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain pre-exposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in future. PMID:26928472

  13. Pro-inflammatory role of Anti-Ro/SSA autoantibodies through the activation of Furin-TACE-amphiregulin axis.

    Science.gov (United States)

    Lisi, Sabrina; Sisto, Margherita; Lofrumento, Dario Domenico; Cucci, Liana; Frassanito, Maria Antonia; Mitolo, Vincenzo; D'Amore, Massimo

    2010-09-01

    Prolonged inflammation can be detrimental because it may cause host toxicity and tissue damage. Indeed, excessive production of inflammatory cytokines is often associated with many autoimmune diseases. In this study we demonstrate that the anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjögren's syndrome. We have discovered that the up-regulation of AREG occurs through TNF-alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating that: (i) TNF-alpha gene silencing provokes a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated healthy SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-alpha-induced IL-6 and IL-8 secretion in healthy SGEC treated with anti-Ro/SSA Abs. These findings indicate that TACE-mediated AREG shedding plays a critical role in TNF-alpha-induced IL-6 and IL-8 secretion by the human healthy salivary gland epithelial cells, suggesting that this may be one of the possible intracellular mechanisms involved in the salivary glands inflammatory response in Sjögren's syndrome.

  14. Suppressive Activity of a Macrolide Antibiotic, Roxithromycin, on Pro-Inflammatory Cytokine Production in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    H. Suzaki

    1999-01-01

    Full Text Available This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM, on the production of pro-inflammatory cytokines, interleukin (IL-1β and tumor necrosis factor (TNF-α. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1β and TNF-α contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1β and TNF-α in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 μg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1β and TNF-α in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1β and TNF-α in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.

  15. Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells.

    Science.gov (United States)

    Li, Li; Zhang, Xiao-Hui; Liu, Guang-Rong; Liu, Chang; Dong, Yin-Mao

    2016-06-01

    Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions. PMID:27473957

  16. Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells

    Institute of Scientific and Technical Information of China (English)

    LI Li; ZHANG Xiao-Hui; LIU Guang-Rong; LIU Chang; DONG Yin-Mao

    2016-01-01

    Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm.Both cell types are involved in a variety of inflammatory and immune events,producing an array of inflammatory mediators,such as cytokines.The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation.The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI).The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays.Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels.Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines,such as interleukin (IL)-6,IL-8,IL-1β,and tumor necrosis factor (TNF)-α.The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK),revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition.Furthermore,isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells.In conclusion,the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.

  17. MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG.

    Science.gov (United States)

    Garg, Rohini; Akhade, Ajay Suresh; Yadav, Jitender; Qadri, Ayub

    2015-10-01

    Vi capsular polysaccharide is currently in use as a vaccine against human typhoid caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs. We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex. In the present study, we show that immunization with Vi produces IgM as well as IgG Abs in wild type mice. This ability is not compromised in mice deficient in T cells. However, immunization of mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine might be vital in generating IgG Abs with this T-independent Ag.

  18. Antimicrobial activity of antiproteinases.

    Science.gov (United States)

    Sallenave, J M

    2002-04-01

    Low-molecular-mass neutrophil elastase inhibitors have been shown to be important in the control of lung inflammation. In addition to inhibiting the enzyme neutrophil elastase, these low-molecular-mass compounds (10 kDa) have been shown to have other activities. For example, secretory leucocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor/SKALP (skin-derived antileucoproteinase)/elafin have also been shown to have "defensin"-like antimicrobial activities. Indeed, these inhibitors have antimicrobial properties in vitro against bacteria, fungi and, potentially, HIV. In addition, we have shown, using an adenovirus-mediated gene transfer overexpression strategy, that elafin is also active against Pseudomonas aeruginosa infection in mice in vivo. The mechanism of action is currently under investigation. In addition to these direct or indirect effects on microbes, it has been shown that lipopolysaccharide is able to up-regulate SPLI production in macrophages in vitro, and that the addition of recombinant SLPI to human monocytes or the transfection of macrophages with SPLI can down-regulate pro-inflammatory mediators such as tumour necrosis factor, presumably to limit self-damaging excessive inflammation. Using viral gene transfer vectors, we are currently investigating the potential of these inhibitors in various models of inflammation in vivo. PMID:12023836

  19. Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-kappaB activation and pro-inflammatory gene expression in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Haller, D.; Holt, L.; Parlesak, Alexandr;

    2004-01-01

    We have previously shown that non-pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)-kappaB transcriptional activity and pro-inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechani...

  20. Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

    Directory of Open Access Journals (Sweden)

    Lopez-Lastra Marcelo

    2011-05-01

    Full Text Available Abstract Background Andes virus (ANDV, a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9 that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC. Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs

  1. PGH1, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP2.

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    Ralf Schröder

    Full Text Available Prostaglandin H(1 (PGH(1 is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA and the precursor for the 1-series of prostaglandins which are often viewed as "anti-inflammatory". Herein we present evidence that PGH(1 is a potent activator of the pro-inflammatory PGD(2 receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca(2+ flux studies reveal that PGH(1 activates CRTH2 as PGH(2, PGD(2 or PGD(1 do. The PGH(1 precursor DGLA and the other PGH(1 metabolites did not display such effect. PGH(1 specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH(1 is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH(1 mediates migration of and Ca(2+ flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH(1 as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase.

  2. A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide.

    Directory of Open Access Journals (Sweden)

    Christine Wittmann

    Full Text Available Tissue injury and infection trigger innate immune responses. However, dysregulation may result in chronic inflammation and is commonly treated with corticosteroids and non-steroidal anti-inflammatory drugs. Unfortunately, long-term administration of both therapeutic classes can cause unwanted side effects. To identify alternative immune-modulatory compounds we have previously established a novel screening method using zebrafish larvae. Using this method we here present results of an in vivo high-content drug-repurposing screen, identifying 63 potent anti-inflammatory drugs that are in clinical use for other indications. Our approach reveals a novel pro-inflammatory role of nitric oxide. Nitric oxide affects leukocyte recruitment upon peripheral sensory nervous system or epithelial injury in zebrafish larvae both via soluble guanylate cyclase and in a soluble guanylate cyclase -independent manner through protein S-nitrosylation. Together, we show that our screening method can help to identify novel immune-modulatory activities and provide new mechanistic insights into the regulation of inflammatory processes.

  3. (1→6)- and (1→3)(1→6)-β-glucans from Lasiodiplodia theobromae MMBJ: Structural characterization and pro-inflammatory activity.

    Science.gov (United States)

    Oliveira, Kassandra S M; Di Bastiani, Mirela; Cordeiro, Lucimara M C; Costa, Mírian F; Toledo, Karina A; Iacomini, Marcello; Babosa, Aneli M; Dekker, Robert F H; Nascimento, Valéria M G

    2015-11-20

    The chemical composition and structural characterization of exopolysaccharides from the fungus Lasiodiplodia theobromae MMBJ are described, and the immunomodulatory activity of a purified β-glucan was evaluated. L. theobromae MMBJ produced three different β-glucans. One, fraction PEPS, was a branched (1→3)(1→6)-β-glucan and was insoluble in cold water. The other two, fractions SEPS-005R and SEPS-10E, were characterized as linear (1→6)-β-glucans with molar mass of 1.8×10(6)Da and 7.0×10(3)Da, respectively. From a total of 2.2g/L of EPS produced by L. theobromae through submerged fermentation, 1.5g/L (67%) was of the branched (1→3)(1→6)-β-glucan, while 25% (w/w) were linear (1→6)-β-glucans. Tests conducted with macrophages showed that the high molar mass (1→6)-β-glucan fraction (SEPS-005R) induced a pro-inflammatory response pattern. PMID:26344312

  4. Aggressive re-warming at 38.5 °C following deep hypothermia at 21 °C increases neutrophil membrane bound elastase activity and pro-inflammatory factor release

    OpenAIRE

    Tang, Min; Zhao, Xiao-gang; He, Yi; Gu, John Yan; Mei, Ju

    2016-01-01

    Background Cardiopulmonary bypass (CPB) is often performed under hypothermic condition. The effects of hypothermia and re-warming on neutrophil activity are unclear. This study aimed to compare the effects of different hypothermia and re-warming regimens on neutrophil membrane bound elastase (MBE) activity and the release of pro-inflammatory factors from neutrophils. Methods Human neutrophils were exposed to different hypothermia and re-warming regimens. MBE activity and the release of interl...

  5. Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2

    NARCIS (Netherlands)

    Plantinga, T.S.; Crisan, T.O.; Oosting, M.; Veerdonk, F.L. van de; Jong, D.J. de; Philpott, D.J.; Meer, J.W. van der; Girardin, S.E.; Joosten, L.A.B.; Netea, M.G.

    2011-01-01

    OBJECTIVE: Autophagy has recently been shown to modulate the production of pro-inflammatory cytokine production and to contribute to antigen processing and presentation through the major histocompatibility complex. Genetic variation in the autophagy gene ATG16L1 has been recently implicated in Crohn

  6. ß-Hydroxybutyrate Activates the NF-κB Signaling Pathway to Promote the Expression of Pro-Inflammatory Factors in Calf Hepatocytes

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    Xiaoxia Shi

    2014-01-01

    Full Text Available Background/Aims: ß-hydroxybutyrate (BHBA is the major component of ketone bodies in ketosis. Dairy cows with ketosis often undergo oxidative stress. BHBA is related to the inflammation involved in other diseases of dairy cattle. However, whether BHBA can induce inflammatory injury in dairy cow hepatocytes and the potential mechanism of this induction are not clear. The NF-κB pathway plays a vital role in the inflammatory response. Methods: Therefore, this study evaluated the oxidative stress, pro-inflammatory factors and NF-κB pathway in cultured calf hepatocytes treated with different concentrations of BHBA, pyrrolidine dithiocarbamate (PDTC, an NF-κB pathway inhibitor and N-acetylcysteine (NAC, antioxidant. Results: The results showed that BHBA could significantly increase the levels of oxidation indicators (MDA, NO and iNOS, whereas the levels of antioxidation indicators (GSH-Px, CAT and SOD were markedly decreased in hepatocytes. The IKKß activity and phospho-IκBa (p-IκBa contents were increased in BHBA-treated hepatocytes. This increase was accompanied by the increased expression level and transcription activity of p65. The expression levels of NF-κB-regulated inflammatory cytokines, namely TNF-a, IL-6 and IL-1ß, were markedly increased after BHBA treatment, while significantly decreased after NAC treatment. However, the p-IκBa level and the expression and activity of p65 and its target genes were markedly decreased in the PDTC + BHBA group compared with the BHBA (1.8 mM group. Moreover, immunocytofluorescence of p65 showed a similar trend. Conclusion: The present data indicate that higher concentrations of BHBA can induce cattle hepatocyte inflammatory injury through the NF-κB signaling pathway, which may be activated by oxidative stress.

  7. Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA.

    Science.gov (United States)

    Sampey, Gavin C; Saifuddin, Mohammed; Schwab, Angela; Barclay, Robert; Punya, Shreya; Chung, Myung-Chul; Hakami, Ramin M; Zadeh, Mohammad Asad; Lepene, Benjamin; Klase, Zachary A; El-Hage, Nazira; Young, Mary; Iordanskiy, Sergey; Kashanchi, Fatah

    2016-01-15

    HIV-1 infection results in a chronic illness because long-term highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/μl were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-β, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5' and 3' stems (TAR microRNAs) bound best to TLR7 and -8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF-κB pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART.

  8. Effect of probiotics on pro-inflammatory cytokines and NF-κB activation in ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Sahar; K; Hegazy; Mohamed; M; El-Bedewy

    2010-01-01

    AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbr...

  9. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells

    OpenAIRE

    Yuan Shi-Ying; Zhou Jie-Ping; Liu Ren-Gang; Zheng Jin; Li Long-Yan; Wu Yan; Wang Yan-Ping; Shang You; Yao Shang-Long

    2011-01-01

    Abstract Background Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells. Methods BV-2 cells were treated with ...

  10. Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress.

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    Zhenying Han

    Full Text Available Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1 and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, α-7 nAchR agonist, methyllycaconitine (MLA, nAchR antagonist, or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO. Behavior test, lesion volume, CD68(+, M1 (CD11b(+/Iba1(+ and M2 (CD206/Iba1+ microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68(+ and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in α-7 nAchR neuro-protective effect.

  11. Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-kappaB activation and pro-inflammatory gene expression in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Haller, D.; Holt, L.; Parlesak, Alexandr;

    2004-01-01

    We have previously shown that non-pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)-kappaB transcriptional activity and pro-inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechanism...... of immune-epithelial cell cross-talk on Gram-negative enteric bacteria-induced NF-kappaB signalling and pro-inflammatory gene expression in IEC using HT-29/MTX as well as CaCO-2 transwell cultures Interestingly, while differentiated HT-29/MTX cells are unresponsive to non-pathogenic Gram negative bacterial...... in the presence of PBMC. Interestingly, B. vulgatus- and E. coli-derived lipopolysaccharide-induced similar IL-8 mRNA expression in epithelial cells after basolateral stimulation of HT-29/PBMC cocultures. Although luminal enteric bacteria have adjuvant and antigenic properties in chronic intestinal inflammation...

  12. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    International Nuclear Information System (INIS)

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  13. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

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    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  14. Naegleria fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation.

    Science.gov (United States)

    Cervantes-Sandoval, Isaac; Serrano-Luna, José de Jesús; Meza-Cervantez, Patricia; Arroyo, Rossana; Tsutsumi, Víctor; Shibayama, Mineko

    2009-11-01

    Naegleria fowleri is an amoeboflagellate responsible for the fatal central nervous system (CNS) disease primary amoebic meningoencephalitis (PAM). This amoeba gains access to the CNS by invading the olfactory mucosa and crossing the cribriform plate. Studies using a mouse model of infection have shown that the host secretes mucus during the very early stages of infection, and this event is followed by an infiltration of neutrophils into the nasal cavity. In this study, we investigated the role of N. fowleri trophozoites in inducing the expression and secretion of airway mucin and pro-inflammatory mediators. Using the human mucoepidermal cell line NCI-H292, we demonstrated that N. fowleri induced the expression of the MUC5AC gene and protein and the pro-inflammatory mediators interleukin-8 (IL-8) and interleukin-1 beta (IL-1 beta), but not tumour necrosis factor-alpha or chemokine c-c motif ligand 11 (eotaxin). Since the production of reactive oxygen species (ROS) is a common phenomenon involved in the signalling pathways of these molecules, we analysed if trophozoites were capable of causing ROS production in NCI-H292 cells by detecting oxidation of the fluorescent probe 2,7-dichlorofluorescein diacetate. NCI-H292 cells generated ROS after 15-30 min of trophozoite stimulation. Furthermore, the expression of MUC5AC, IL-8 and IL-1 beta was inhibited in the presence of the ROS scavenger DMSO. In addition, the use of an epidermal growth factor receptor inhibitor decreased the expression of MUC5AC and IL-8, but not IL-1 beta. We conclude that N. fowleri induces the expression of some host innate defence mechanisms, such as mucin secretion (MUC5AC) and local inflammation (IL-8 and IL-1 beta) in respiratory epithelial cells via ROS production and suggest that these innate immune mechanisms probably prevent most PAM infections.

  15. The Pro-inflammatory Effects of Glucocorticoids in the Brain.

    Science.gov (United States)

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein-protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  16. Circulating Endothelial-Derived Apoptotic Microparticles in the Patients with Ischemic Symptomatic Chronic Heart Failure: Relevance of Pro-Inflammatory Activation and Outcomes

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    Alexander E. Berezin

    2014-09-01

    Full Text Available Background: Endothelial-derived apoptotic microparticles (EMPs play a pivotal role in endothelial dysfunction in hronic Heart Failure (CHF. Objectives: The present study aimed to evaluate the association between EMPs and pro-inflammatory biomarkers, clinical status, and outcomes in the patients with ischemic CHF. Patients and Methods: This study was conducted on 154 patients with ischemic symptomatic moderate-to-severe CHF on discharge from hospital. The observation period was up to 3 years. Circulating NT-pro-BNP, TNF-alpha, sFas, and sFas ligand were determined at baseline. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-re-hospitalization rate were examined. The data were analyzed using descriptive statistics, Receive Operation Characteristic Curve (ROC, and logistic regression analysis. Besides, P 0.514 n/mL and those with a low level of the biomarker (< 0.514 n/mL regarding their survival. The number of circulating EPMs independently predicted all-cause mortality (OR = 1.58; 95% CI = 1.20 – 1.88; P = 0.001, CHF-related death (OR = 1.22; 95% CI: 1.12 – 1.36; P < 0.001, and CHF-related re-hospitalization (OR = 1.20; 95% CI: 1.11 – 1.32; P < 0.001. Conclusions: Among the patients with symptoms of CHF, increased number of circulating EMPs was associated with increased 3-year CHF-related death, all-cause mortality, and risk of recurrent hospitalization due to CHF.

  17. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia

    Institute of Scientific and Technical Information of China (English)

    Cheng-yun JIN; Jae-dong LEE; Cheol PARK; Yung hyun CHOI; Gi-young KIM

    2007-01-01

    Aim: Pro-inflammatory mediators, such as prostaglandin E2 (PGE2) and nitric oxide(NO), and pro-inflammatory cytokines such as intedeukini(IL)- 1β, IL-6, and TNF-α, play pivotal roles in brain injuries. The anti-inflammatory properties are known to be associated with significant reductions in pro-inflammatory mediators in brain injuries. In the present study we investigate whether the effects of curcumin on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimu-lated BV2 microglia. Methods: Curcumin were administered and their effects on LPS-induced pro-inflammatory mediators were monitored by Western blotting and RT-PCR. Result: Curcumin significantly inhibited the release of NO, PGE2,and pro-inflammatory cytokines in a dose-dependent manner. Curcumin also attenuated the expressions of inducible NO synthase and cyclooxygenase-2 mRNA and protein levels. Moreover, curcumin suppressed NF-κB activation via the translocation of p65 into the nucleus. Our data also indicate that curcumin exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes through the NF-rd3 signaling pathway. Conclusion: Anti-inflam-matory properties of curcumin may be useful for treating the inflammatory and deleterious effects of microglial activation in response to LPS stimulation.

  18. Fish and mammalian phagocytes differentially regulate pro-inflammatory and homeostatic responses in vivo.

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    Aja M Rieger

    Full Text Available Phagocytosis is a cellular mechanism that is important to the early induction of antimicrobial responses and the regulation of adaptive immunity. At an inflammatory site, phagocytes serve as central regulators for both pro-inflammatory and homeostatic anti-inflammatory processes. However, it remains unclear if this is a recent evolutionary development or whether the capacity to balance between these two seemingly contradictory processes is a feature already displayed in lower vertebrates. In this study, we used murine (C57BL/6 and teleost fish (C. auratus in vitro and in vivo models to assess the evolutionary conservation of this dichotomy at a site of inflammation. At the level of the macrophage, we found that teleost fish already displayed divergent pro-inflammatory and homeostatic responses following internalization of zymosan or apoptotic bodies, respectively, and that these were consistent with those of mice. However, fish and mice displayed significant differences in vivo with regards to the level of responsiveness to zymosan and apoptotic bodies, the identity of infiltrating leukocytes, their rate of infiltration, and the kinetics and strength of resulting antimicrobial responses. Unlike macrophages, significant differences were identified between teleost and murine neutrophilic responses. We report for the first time that activated murine, but not teleost neutrophils, possess the capacity to internalize apoptotic bodies. This internalization translates into reduction of neutrophil ROS production. This may play an important part in the recently identified anti-inflammatory activity that mammalian neutrophils display during the resolution phase of inflammation. Our observations are consistent with continued honing of inflammatory control mechanisms from fish to mammals, and provide added insights into the evolutionary path that has resulted in the integrated, multilayered responses that are characteristic of higher vertebrates.

  19. Store-operated calcium channels and pro-inflammatory signals

    Institute of Scientific and Technical Information of China (English)

    Wei-chiao CHANG

    2006-01-01

    In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endothelia and epithelia,the major pathway for calcium(Ca2+)entry is through store-operated Ca2+ channels in the plasma membrane.These channels are activated by the emptying of intracellular Ca2+ stores,however,neither the gating mechanism nor the downstream targets of these channels has been clear established.Here,I review some of the proposed gating mechanisms of store-operated Ca2+ channels and the functional implications in regulating pro-inflammatory signals.

  20. Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways.

    Science.gov (United States)

    Kral, Julia Barbara; Kuttke, Mario; Schrottmaier, Waltraud Cornelia; Birnecker, Birgit; Warszawska, Joanna; Wernig, Christina; Paar, Hannah; Salzmann, Manuel; Sahin, Emine; Brunner, Julia Stefanie; Österreicher, Christoph; Knapp, Sylvia; Assinger, Alice; Schabbauer, Gernot

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with limited treatment options. Additionally, the lack of a complete understanding of underlying immunological mechanisms underscores the importance of discovering novel options for therapeutic intervention. Since the PI3K/PTEN pathway in myeloid cells influences their effector functions, we wanted to elucidate how sustained PI3K activity induced by cell-type specific genetic deficiency of its antagonist PTEN modulates IPF, in a murine model of bleomycin-induced pulmonary fibrosis (BIPF). We found that myeloid PTEN deficient mice (PTEN(MyKO)), after induction of BIPF, exhibit increased TGF-β1 activation, mRNA expression of pro-collagens and lysyl oxidase as well as augmented collagen deposition compared to wild-type littermates, leading to enhanced morbidity and decreased survival. Analysis of alveolar lavage and lung cell composition revealed that PTEN(MyKO) mice exhibit reduced numbers of macrophages and T-cells in response to bleomycin, indicating an impaired recruitment function. Interestingly, we found dysregulated macrophage polarization as well as elevated expression and release of the pro-fibrotic cytokines IL-6 and TNF-α in PTEN(MyKO) mice during BIPF. This might point to an uncontrolled wound healing response in which the inflammatory as well as tissue repair mechanisms proceed in parallel, thereby preventing resolution and at the same time promoting extensive fibrosis. PMID:26971883

  1. Neu1 sialidase and matrix metalloproteinase-9 cross-talk regulates nucleic acid-induced endosomal TOLL-like receptor-7 and -9 activation, cellular signaling and pro-inflammatory responses.

    Science.gov (United States)

    Abdulkhalek, Samar; Szewczuk, Myron R

    2013-11-01

    The precise mechanism(s) by which intracellular TOLL-like receptors (TLRs) become activated by their ligands remains unclear. Here, we report a molecular organizational G-protein coupled receptor (GPCR) signaling platform to potentiate a novel mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B GPCR, all of which form a tripartite complex with TLR-7 and -9. siRNA silencing Neu1, MMP-9 and neuromedin-B GPCR in RAW-blue macrophage cells significantly reduced TLR7 imiquimod- and TLR9 ODN1826-induced NF-κB (NF-κB-pSer(536)) activity. Tamiflu, specific MMP-9 inhibitor, neuromedin B receptor specific antagonist BIM23127, and the selective inhibitor of whole heterotrimeric G-protein complex BIM-46174 significantly block nucleic acid-induced TLR-7 and -9 MyD88 recruitment, NF-κB activation and proinflammatory TNFα and MCP-1 cytokine responses. For the first time, Neu1 clearly plays a central role in mediating nucleic acid-induced intracellular TLR activation, and the interactions involving NMBR-MMP9-Neu1 cross-talk constitute a novel intracellular TLR signaling platform that is essential for NF-κB activation and pro-inflammatory responses. PMID:23827939

  2. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  3. Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

    Science.gov (United States)

    Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

    2016-02-01

    Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases. PMID:26276128

  4. Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

    OpenAIRE

    Búfalo, Michelle Cristiane; Ferreira, Isabel; Costa, Gustavo; Francisco, Vera; Liberal, Joana; Cruz, Maria Teresa; Lopes, Maria Celeste; Batista, Maria Teresa; Sforcin, José Maurício

    2013-01-01

    Ethnopharmacological relevance Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities. It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action. Thus, the goal of this study was to verify the antioxidant activity and to explore the anti-inflammatory properties of propolis by addressing its i...

  5. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Zhang

    Full Text Available BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT carriers and 78 immune activated (IA patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+ subsets, which were closely associated with serum alanine aminotransferase (ALT levels and the liver histological activity index (HAI scores. In addition, the increased CD16(+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(- monocytes/macrophages. Furthermore, peripheral blood CD16(+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.

  6. Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

    OpenAIRE

    Li, Hai-Yan; Pan, Lang; Ke, Yue-shuang; Batnasan, Enkhzaya; Jin, Xiang-qun; Liu, Zhong-Ying; Ba, Xue-qing

    2014-01-01

    Aim: Daidzein (4′,7-dihydroxyisoflavone) is an isoflavone exiting in many herbs that has shown anti-inflammation activity. The aim of this study was to investigate the mechanism underlying its anti-inflammatory action in murine lung epithelial cells. Methods: C57BL/6 mice were intranasally exposed to TNF-α to induce lung inflammation. The mice were injected with daidzein (400 mg/kg, ip) before TNF-α challenge, and sacrificed 12 h after TNF-α challenge, and lung tissues were collected for anal...

  7. Macrophage-associated mesenchymal stem cells assume an activated, migratory, pro-inflammatory phenotype with increased IL-6 and CXCL10 secretion.

    Directory of Open Access Journals (Sweden)

    Kevin Anton

    Full Text Available Mesenchymal stem cells (MSCs exhibit tropism for sites of tissue injury and tumors. However, the influence of the microenvironment on MSC phenotype and localization remains incompletely characterized. In this study, we begin to define a macrophage-induced MSC phenotype. These MSCs secrete interleukin-6 (IL-6, CCL5, and interferon gamma-induced protein-10 (CXCL10 and exhibit increased mobility in response to multiple soluble factors produced by macrophages including IL-8, CCL2, and CCL5. The pro-migratory phenotype is dependent on activation of a c-Jun N-terminal kinase (JNK pathway. This work begins to identify the influence of macrophages on MSC biology. These interactions are likely to play an important role in the tissue inflammatory response and may provide insight into the migratory potential of MSCs in inflammation and tissue injury.

  8. Dinamic changes of pro-inflammatory cytokines, adhesion molecules and lymphocytes activation markers as early indicators of diseases severity in patients with Dengue

    Directory of Open Access Journals (Sweden)

    Silvana Vielma

    2014-09-01

    Full Text Available Several immunopathogenic mechanisms have been proposed to explain the massive increase of vascular permeability observed in the severe forms of infection by Dengue Virus (DENV. Our aim was to determine the kinetic changes of inflammatory mediators (IL-8, TNF- α, soluble early lymphocyte activation markers (sIL-2R, sTNF-Rp75 and soluble fractions of cell adhesion molecules (sICAM-1 and sVCAM-1 as indicators for early recognition of disease severity in patients with laboratory-confirmed dengue. Twenty patients classified as Dengue±Warning Signs (D±WS and thirty patients with Severe Dengue (SD were included in the study. Serums of apparently healthy individuals were included as controls. Compared with normal subjects, D±WS cases did not show significant differences in the levels of IL-8 or TNF-α during the acute nor in the critical stages of the disease; however, in D±WS cases levels of sICAM-1 and sVCAM-1 were higher than controls during both phases; in contrast, significant increase of sTNF-p75 and sIL2R levels were observed during the critical phase of the disease. Compared with both dengue patients and controls, patients with SD showed significant rise in the levels of IL-8 and TNF-α during the critical phase of the disease and a significant increase in adhesion molecules were detected in both phases, but the highest levels of sVCAM-1 and sIL-2R were observed only during the acute stage of the disease. In conclusion, sIL-2R and sVCAM-1, as early markers of lymphocyte and endothelial activation, would serves as indicators of severity during the acute phase of dengue infection.

  9. A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein.

    Science.gov (United States)

    Sánchez Vallecillo, María F; Minguito de la Escalera, María M; Aguirre, María V; Ullio Gamboa, Gabriela V; Palma, Santiago D; González-Cintado, Leticia; Chiodetti, Ana L; Soldano, Germán; Morón, Gabriel; Allemandi, Daniel A; Ardavín, Carlos; Pistoresi-Palencia, María C; Maletto, Belkys A

    2015-09-28

    Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that the whole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design. PMID:26188153

  10. A high-mobility group box 1 that binds to DNA, enhances pro-inflammatory activity, and acts as an anti-infection molecule in black rockfish, Sebastes schlegelii.

    Science.gov (United States)

    Xin-Peng, Zhao; Yong-Hua, Hu; Yong, Liu; Jing-Jing, Wang; Guang-Hua, Wang; Ren-Jie, Wang; Min, Zhang

    2016-09-01

    High-mobility group box (HMGB) 1 is a chromosomal protein that plays critical roles in DNA transcription, replication and repair. In addition, HMGB1 functions as a pro-inflammatory molecule in many vertebrates and invertebrates. In teleosts, very limited studies of HMGB1 have been reported. In this study, we identified a HMGB1 homologue (SsHMGB1) from black rockfish (Sebastes schlegelii) and analyzed its structure, expression and biological function. The open reading frame of SsHMGB1 is 621 bp, with a 5'-untranslated region (UTR) of 62 bp and a 3'-UTR of 645 bp. SsHMGB1 contains two typical HMG boxes and an acidic C-terminal tail. The deduced amino acid sequence of SsHMGB1 shares the highest overall identity (89.4%) with the HMGB1 of Anoplopoma fimbria. The expression of SsHMGB1 occurred in multiple tissues and was highest in the brain. Moreover, the mRNA level of SsHMGB1 in head kidney (HK) macrophages could be induced by Listonella anguillarum in a time-dependent manner. Recombinant SsHMGB1 purified from Escherichia coli (i) bound DNA fragments in a dose-dependent manner; and (ii) induced the expression of cytokines in HK macrophages, including a significant increase in TNF-α activity and enhanced mRNA level of TNF13B and IL-1 β, which are known to be involved in antibacterial defense; moreover, (iii) significantly improved the macrophage bactericidal activity together with reduced pathogen dissemination and replication of bacteria in fish kidney. These results indicated that SsHMGB1 is a novel HMGB1 that possesses apparent immunoregulatory properties and is likely to be involved in fighting bacterial infection. PMID:27492120

  11. Blockade of the MEK/ERK pathway with a raf inhibitor prevents activation of pro-inflammatory mediators in cerebral arteries and reduction in cerebral blood flow after subarachnoid hemorrhage in a rat model

    DEFF Research Database (Denmark)

    Maddahi, Aida; Ansar, Saema; Chen, Qingwen;

    2011-01-01

    hours, cerebral arteries were harvested, and iNOS, interleukin (IL)-6, IL-1ß, matrix metalloproteinase (MMP)-9, tissue inhibitors of metalloproteinase (TIMP)-1, and phosphorylated ERK1/2 were investigated by immunofluorescence, real-time polymerase chain reaction (PCR), and Western blot analysis....... Cerebral blood flow (CBF) was measured using autoradiography. Protein levels of MMP-9, TIMP-1, iNOS, IL-6, and IL-1ß were increased after SAH, as were mRNA levels of IL-6, MMP-9, and TIMP-1. After SAH, pERK1/2 was increased, but CBF was reduced. Treatment with SB-386023-b at 0 or 6 hours after SAH...... normalized CBF and prevented SAH-induced upregulation of MMPs, pro-inflammatory cytokines, and pERK1/2 proteins. These results suggested that inhibition of MEK/ERK signal transduction by a specific raf inhibitor administered up to 6 hours after SAH normalized the expression of pro-inflammatory mediators...

  12. Blockade of the MEK/ERK pathway with a raf inhibitor prevents activation of pro-inflammatory mediators in cerebral arteries and reduction in cerebral blood flow after subarachnoid hemorrhage in a rat model

    DEFF Research Database (Denmark)

    Maddahi, Aida; Ansar, Saema; Chen, Qingwen;

    2011-01-01

    hours, cerebral arteries were harvested, and iNOS, interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP)-9, tissue inhibitors of metalloproteinase (TIMP)-1, and phosphorylated ERK1/2 were investigated by immunofluorescence, real-time polymerase chain reaction (PCR), and Western blot analysis....... Cerebral blood flow (CBF) was measured using autoradiography. Protein levels of MMP-9, TIMP-1, iNOS, IL-6, and IL-1β were increased after SAH, as were mRNA levels of IL-6, MMP-9, and TIMP-1. After SAH, pERK1/2 was increased, but CBF was reduced. Treatment with SB-386023-b at 0 or 6 hours after SAH...... normalized CBF and prevented SAH-induced upregulation of MMPs, pro-inflammatory cytokines, and pERK1/2 proteins. These results suggested that inhibition of MEK/ERK signal transduction by a specific raf inhibitor administered up to 6 hours after SAH normalized the expression of pro-inflammatory mediators...

  13. High Antimicrobial Activity and Low Human Cell Cytotoxicity of Core-Shell Magnetic Nanoparticles Functionalized with an Antimicrobial Peptide.

    Science.gov (United States)

    Maleki, Hajar; Rai, Akhilesh; Pinto, Sandra; Evangelista, Marta; Cardoso, Renato M S; Paulo, Cristiana; Carvalheiro, Tiago; Paiva, Artur; Imani, Mohammad; Simchi, Abdolreza; Durães, Luísa; Portugal, António; Ferreira, Lino

    2016-05-11

    Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory concentration (MIC) of the AMP-NP for Escherichia coli was 0.4 μg/mL, 10-times lower than the MIC of soluble CM. The antimicrobial activity of CM depends on the length of the spacer between the CM and the NP. AMP-NPs are taken up by endothelial (between 60 and 170 pg of NPs per cell) and macrophage (between 18 and 36 pg of NPs per cell) cells and accumulate preferentially in endolysosomes. These NPs have no significant cytotoxic and pro-inflammatory activities for concentrations up to 200 μg/mL (at least 100 times higher than the MIC of soluble CM). Our results in membrane models suggest that the selectivity of AMP-NPs for bacteria and not eukaryotic membranes is due to their membrane compositions. The AMP-NPs developed here open new opportunities for infection-site targeting. PMID:27074633

  14. 雷公藤内酯醇对内毒素激活小鼠腹腔巨噬细胞分泌促炎症介质NO和IL-6的影响%Effect of triptolide on lipopolysaccharide-activated secretion of the pro-inflammatory cytokines NO and IL-6 in celiac macrophages of mice

    Institute of Scientific and Technical Information of China (English)

    杨帆; 胡耑; 白祥军

    2011-01-01

    Objective Tripterygium wilfordii Hook. f. has been used for centuries in traditional Chinese medicine to treat autoimmune disease associated with increased production of the pro-inflammatory cytokine. Triptolide( TP) is a compound originally purified from T. wilfordii Hook f. and it has potent anti- inflammatory and immunosuppressant activities. In this study, we investigated the effect of TP on secretion of NO and IL-6 in celiac macrophages ( MΦ) activated by lipopolysaccharide ( LPS) in Kunming mice. Methods Celiac MΦ of mice were separated, purified, and activated by LPS, then cultured in vitro with TP of different concentrations. The level of NO in cellular supematants was determined by Griess reagent, and that of IL-6 was determined by ELISA. Results We found that pro-inflammatory cytokine NO activity in MΦ induced by LPS was significantly inhibited by TP ( 10-3-10 μg/ml) from 4-24 h in a time and dose- dependent manner (P < 0. 01). The level of IL-6 in MΦ was significantly inhibited by TP (10-3-10 μg/ml) at 12 h in a dose-dependent manner (P <0. 01). Conclusions We demonstrated that TP can inhibit levels of NO and IL-6 in celiac MΦ of Kunming mice activated by LPS.

  15. Bromelain Treatment Decreases Secretion of Pro-Inflammatory Cytokines and Chemokines by Colon Biopsies In Vitro

    OpenAIRE

    Onken, Jane E.; Greer, Paula K.; Calingaert, Brian; Hale, Laura P.

    2007-01-01

    Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding pro-inflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn’s disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. ...

  16. Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction.

    Science.gov (United States)

    Hermanns, Heike M; Wohlfahrt, Julia; Mais, Christine; Hergovits, Sabine; Jahn, Daniel; Geier, Andreas

    2016-08-01

    The pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) are key players of the innate and adaptive immunity. Their activity needs to be tightly controlled to allow the initiation of an appropriate immune response as defense mechanism against pathogens or tissue injury. Excessive or sustained signaling of either of these cytokines leads to severe diseases, including rheumatoid arthritis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis), steatohepatitis, periodic fevers and even cancer. Studies carried out in the last 30 years have emphasized that an elaborate control system for each of these cytokines exists. Here, we summarize what is currently known about the involvement of receptor endocytosis in the regulation of these pro-inflammatory cytokines' signaling cascades. Particularly in the last few years it was shown that this cellular process is far more than a mere feedback mechanism to clear cytokines from the circulation and to shut off their signal transduction. PMID:27071147

  17. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada); Klegeris, Andis [Department of Biology, University of British Columbia Okanagan, Kelowna, BC (Canada); Little, Jonathan P., E-mail: jonathan.little@ubc.ca [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada)

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  18. Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

    Directory of Open Access Journals (Sweden)

    MI Oliveira

    2012-07-01

    Full Text Available Macrophages and dendritic cells (DC share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch, with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

  19. Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

    Directory of Open Access Journals (Sweden)

    F. Morceau

    2009-01-01

    Full Text Available Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway, without erythropoietin defect. This suggested that pro-inflammatory cytokine-mediated signaling pathways affect erythropoietin activity. They could interfere with erythropoietin-mediated signaling pathways, inducing early apoptosis and perturbing the expression and regulation of specific transcription factors involved in the control of erythroid differentiation. In this review we summarize the effect of tumor necrosis factor (TNFα, TNF-related apoptosis-inducing ligand (TRAIL, and interferon (IFN-γ on erythropoiesis with a particular interest for molecular feature.

  20. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes.

    Directory of Open Access Journals (Sweden)

    Gabriella Passacquale

    Full Text Available BACKGROUND: Activated platelets exert a pro-inflammatory action that can be largely ascribed to their ability to interact with leukocytes and modulate their activity. We hypothesized that platelet activation and consequent formation of monocyte-platelet aggregates (MPA induces a pro-inflammatory phenotype in circulating monocytes. METHODOLOGY/PRINCIPAL FINDINGS: CD62P(+ platelets and MPA were measured, and monocytes characterized, by whole blood flow cytometry in healthy subjects, before and two days after receiving influenza immunization. Three monocytic subsets were identified: CD14(+CD16(-, CD14(highCD16(+and CD14(lowCD16(+. The increase in high sensitivity C-reactive protein post-immunization was accompanied by increased platelet activation and MPA formation (25.02±12.57 vs 41.48±16.81; p = 0.01, along with enhancement of circulating CD14(highCD16(+ cells (4.7±3.6 vs 10.4±4.8; p = 0.003, their percentage being linearly related to levels of CD62P(+-platelets (r(2 = 0.4347; p = 0.0008. In separate in vitro experiments, co-incubation of CD14(+CD16(- cells, isolated from healthy donor subjects, with autologous platelets gave rise to up-regulation of CD16 on monocytes as compared with those maintained in medium alone (% change in CD14(+CD16(+ cells following 48 h co-incubation of monocytes with platelets was +106±51% vs monocytes in medium alone; p<0.001. This effect correlated directly with degree of MPA formation (r(2 = 0.7731; p<0.0001 and was associated with increased monocyte adhesion to endothelial cells. P-selectin glycoprotein ligand-1 (PSGL-1 blocking antibody, which abrogates MPA formation, abolished these effects, as did the cyclooxygenase (COX-2 selective inhibitor NS-398, aspirin and the EP1/EP2-selective antagonist AH6809. CONCLUSIONS/SIGNIFICANCE: These data suggest that MPA formation, as occurs in the blood under pro-inflammatory conditions, expands the pool of circulating CD14(highCD16(+ monocytes in a

  1. IL-1β Receptor Blockade Protects Islets Against Pro-inflammatory Cytokine Induced Necrosis and Apoptosis

    OpenAIRE

    Schwarznau, Alice; Hanson, Matthew S.; Sperger, Jamie M.; Schram, Brian R; Danobeitia, Juan S.; Greenwood, Krista K.; Vijayan, Ashwanth; Fernandez, Luis A.

    2009-01-01

    Pro-inflammatory cytokines (PIC) impair islet viability and function by activating inflammatory pathways that induce both necrosis and apoptosis. The aim of this study was to utilize an in vitro rat islet model to evaluate the efficacy of a clinically approved IL-1 receptor antagonist (Anakinra) in blocking PIC induced islet impairment. Isolated rat islets were cultured for 48h ± PIC (IL-1β, IFNγ, and TNFα and ±IL-1ra then assayed for cellular integrity by flow cytometry, MAPK phosphorylation...

  2. Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells

    Science.gov (United States)

    Nahomi, Rooban B.; Palmer, Allison; Roth, Katelyn E.; Fort, Patrice E.; Nagaraj, Ram H.

    2013-01-01

    The formation of acellular capillaries in the retina, a hallmark feature of diabetic retinopathy, is caused by apoptosis of endothelial cells and pericytes. The biochemical mechanism of such apoptosis remains unclear. Small heat shock proteins play an important role in the regulation of apoptosis. In the diabetic retina, pro-inflammatory cytokines are upregulated. In this study, we investigated the effects of pro-inflammatory cytokines on small heat shock protein 27 (Hsp27) in human retinal endothelial cells (HREC). In HREC cultured in the presence of cytokine mixtures (CM), a significant downregulation of Hsp27 at the protein and mRNA level occurred, with no effect on HSF-1, the transcription factor for Hsp27. The presence of high glucose (25 mM) amplified the effects of cytokines on Hsp27. CM activated indoleamine 2,3-dioxygenase (IDO) and enhanced the production of kynurenine and ROS. An inhibitor of IDO, 1-methyl tryptophan (MT), inhibited the effects of CM on Hsp27. CM also upregulated NOS2 and, consequently, nitric oxide (NO). A NOS inhibitor, L-NAME, and a ROS scavenger blocked the CM-mediated Hsp27 downregulation. While a NO donor in the culture medium did not decrease the Hsp27 content, a peroxynitrite donor and exogenous peroxynitrite did. The cytokines and high glucose-induced apoptosis of HREC were inhibited by MT and L-NAME. Downregulation of Hsp27 by a siRNA treatment promoted apoptosis in HREC. Together, these data suggest that pro-inflammatory cytokines induce the formation of ROS and NO, which, through the formation of peroxynitrite, reduce the Hsp27 content and bring about apoptosis of retinal capillary endothelial cells. PMID:24252613

  3. c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.

    Directory of Open Access Journals (Sweden)

    Victoria Florea

    Full Text Available The proto-oncogene c-Myc is vital for vascular development and promotes tumor angiogenesis, but the mechanisms by which it controls blood vessel growth remain unclear. In the present work we investigated the effects of c-Myc knockdown in endothelial cell functions essential for angiogenesis to define its role in the vasculature. We provide the first evidence that reduction in c-Myc expression in endothelial cells leads to a pro-inflammatory senescent phenotype, features typically observed during vascular aging and pathologies associated with endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation and tube formation. These functional defects were associated with morphological changes, increase in senescence-associated-β-galactosidase activity, upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells in G1-phase, indicating that c-Myc knockdown in endothelial cells induces senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed that senescent phenotype was accompanied by significant upregulation of growth factors, adhesion molecules, extracellular-matrix components and remodeling proteins, and a cluster of pro-inflammatory mediators, which include Angptl4, Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines, transcription factors known to be involved in growth control (E2f1, Id1 and Myb were downregulated, while those involved in inflammatory responses (RelB, Stat1, Stat2 and Stat4 were upregulated. Our results demonstrate a novel role for c-Myc in the prevention of vascular pro-inflammatory phenotype, supporting an important physiological function as a central regulator of inflammation and endothelial dysfunction.

  4. Inhibition of pro-inflammatory mediators: role of Bacopa monniera (L.) Wettst.

    Science.gov (United States)

    Viji, Vijayan; Helen, Antony

    2011-10-01

    Bacopa monniera (L.) Wettst is a renowned plant in the Ayurvedic system of medicine. The present study seeks to identify the anti-inflammatory activity of two fractions from the methanolic extract of Bacopa, viz. the triterpenoid and bacoside-enriched fractions. The ability of these two fractions to inhibit the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 was tested using lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells and peritoneal exudate cells in vitro. We found that triterpenoid and bacoside-enriched fractions significantly inhibited LPS-activated TNF-α, IL-6 and nitrite production in mononuclear cells. Significant antioxidant activity was exhibited by the bacoside enriched fraction compared to the triterpenoid fraction. Carrageenan-induced hind paw oedema assay revealed that triterpenoid and bacoside-enriched fractions exerted anti-oedematogenic effect, while in the arthritis model only the triterpenoid fraction exerted an anti-arthritic potential. The present study provides an insight into the ability of Bacopa monniera to inhibit inflammation through modulation of pro-inflammatory mediator release.

  5. Molecular mechanisms of differentiation of murine pro-inflammatory gamma-delta T cell subsets

    Directory of Open Access Journals (Sweden)

    Bruno eSilva-Santos

    2013-12-01

    Full Text Available Gamma-delta (gd T cells are unconventional innate-like lymphocytes that actively participate in protective immunity against tumors and infectious organisms including bacteria, viruses and parasites. However, gd T cells are also involved in the development of inflammatory and autoimmune diseases. gd T cells are functionally characterized by very rapid production of pro-inflammatory cytokines, while also impacting on (slower but long-lasting adaptive immune responses. This makes it crucial to understand the molecular mechanisms that regulate  T cell effector functions. Although they share many similarities with ab T cells, our knowledge of the molecular pathways that control effector functions in gd T cells still lags significantly behind. In this review, we focus on the segregation of interferon-gamma versus interleukin-17 production in murine thymic-derived gd T cell subsets defined by CD27 and CCR6 expression levels. We summarize the most recent studies that disclose the specific epigenetic and transcriptional mechanisms that govern the stability or plasticity of discrete pro-inflammatory gd T cell subsets, whose manipulation may be valuable for regulating (autoimmune responses.

  6. A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shuai [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Lv, Jiaju [Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan 250021 (China); Han, Liping; Ichikawa, Tomonaga; Wang, Wenjuan; Li, Siying [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Wang, Xing Li [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@pathology.ufl.edu [Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275 (United States); Cui, Taixing, E-mail: taixing.cui@uscmed.sc.edu [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Cyld deficiency suppresses pro-inflammatory phenotypic switch of VSMCs. Black-Right-Pointing-Pointer Cyld deficiency inhibits MAPK rather than NF-kB activity in inflamed VSMCs. Black-Right-Pointing-Pointer CYLD is up-regulated in the coronary artery with neointimal hyperplasia. -- Abstract: CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-{kappa}B) pathway. CYLD has been shown to inhibit vascular lesion formation presumably through suppressing NF-{kappa}B activity in vascular cells. However, herein we report a novel role of CYLD in mediating pro-inflammatory responses in vascular smooth muscle cells (VSMCs) via a mechanism independent of NF-{kappa}B activity. Adenoviral knockdown of Cyld inhibited basal and the tumor necrosis factor alpha (TNF{alpha})-induced mRNA expression of pro-inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-{kappa}B transcriptional activity in RASMCs; however, did not affect the TNF{alpha}-induced NF-{kappa}B activity. Intriguingly, the TNF{alpha}-induced I{kappa}B phosphorylation was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased slightly the basal expression levels of I{kappa}B{alpha} and I{kappa}B{beta} proteins, it did not alter the kinetics of TNF{alpha}-induced I{kappa}B protein degradation in RASMCs. These results indicate that CYLD suppresses the basal NF-{kappa}B activity and TNF{alpha}-induced I{kappa}B kinase activation without affecting TNF{alpha}-induced NF-{kappa}B activity in VSMCs. In addition, knocking down of Cyld suppressed TNF{alpha}-induced activation of mitogen activated protein

  7. Minocycline attenuates Aβ oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Aβ fibrils phagocytosis.

    Science.gov (United States)

    El-Shimy, Ismail Amr; Heikal, Ola Ahmed; Hamdi, Nabila

    2015-11-16

    Microglia, the brain innate immune cells, are activated in response to amyloid beta (Aβ) resulting in neuroinflammation in AD brains. Recently, two phenotypes have been described for microglia: the pro-inflammatory classical and the anti-inflammatory alternative. Changes in microglia phenotype that control their phagocytic function are yet to be determined. The highly neurotoxic Aβ oligomers (oAβ) formed at an early disease stage induce pro-inflammatory microglia activation releasing neurotoxic mediators and contributing to neurodegeneration. A novel strategy for AD treatment is to attenuate microglia-induced inflammation while maintaining efficient Aβ clearance. Minocycline effectively crosses the blood-brain barrier and has widely reported neuroprotective effects. Yet, its exact mechanism of neuroprotection and its effects on microglia are still unknown. The aim of this study is to investigate the effect of minocycline on the phagocytic uptake of fAβ by primary microglia in relation to their activation state in an inflammatory milieu generated by oAβ or LPS. The study shows that minocycline is able to attenuate oAβ-induced neuroinflammatory response of microglia by inhibiting their pro-inflammatory phenotype activation. In addition, a significant enhancement of fAβ phagocytosis by minocycline- treated microglia is reported for the first time, providing novel insight into its neuroprotective role in AD.

  8. Automation of antimicrobial activity screening.

    Science.gov (United States)

    Forry, Samuel P; Madonna, Megan C; López-Pérez, Daneli; Lin, Nancy J; Pasco, Madeleine D

    2016-03-01

    Manual and automated methods were compared for routine screening of compounds for antimicrobial activity. Automation generally accelerated assays and required less user intervention while producing comparable results. Automated protocols were validated for planktonic, biofilm, and agar cultures of the oral microbe Streptococcus mutans that is commonly associated with tooth decay. Toxicity assays for the known antimicrobial compound cetylpyridinium chloride (CPC) were validated against planktonic, biofilm forming, and 24 h biofilm culture conditions, and several commonly reported toxicity/antimicrobial activity measures were evaluated: the 50 % inhibitory concentration (IC50), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC). Using automated methods, three halide salts of cetylpyridinium (CPC, CPB, CPI) were rapidly screened with no detectable effect of the counter ion on antimicrobial activity. PMID:26970766

  9. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.

    Science.gov (United States)

    Papa, Simonetta; Caron, Ilaria; Erba, Eugenio; Panini, Nicolò; De Paola, Massimiliano; Mariani, Alessandro; Colombo, Claudio; Ferrari, Raffaele; Pozzer, Diego; Zanier, Elisa R; Pischiutta, Francesca; Lucchetti, Jacopo; Bassi, Andrea; Valentini, Gianluca; Simonutti, Giulio; Rossi, Filippo; Moscatelli, Davide; Forloni, Gianluigi; Veglianese, Pietro

    2016-01-01

    Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI.

  10. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.

    Science.gov (United States)

    Papa, Simonetta; Caron, Ilaria; Erba, Eugenio; Panini, Nicolò; De Paola, Massimiliano; Mariani, Alessandro; Colombo, Claudio; Ferrari, Raffaele; Pozzer, Diego; Zanier, Elisa R; Pischiutta, Francesca; Lucchetti, Jacopo; Bassi, Andrea; Valentini, Gianluca; Simonutti, Giulio; Rossi, Filippo; Moscatelli, Davide; Forloni, Gianluigi; Veglianese, Pietro

    2016-01-01

    Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI. PMID:26474039

  11. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mar; Troya, María; Padilla, Sabino; Orive, Gorka

    2015-01-01

    One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

  12. A study of the association between type A behavior pattern and activity of catecholamine/NF-KB/pro-inflammatory cytokines in young persons%青年人群A型行为与儿茶酚胺/核因子κB/促炎因子通路的关系

    Institute of Scientific and Technical Information of China (English)

    宁淑娥; 曲鹏; 魏刚; 宗大飞; 张兴; 隋政; 郑美丽

    2011-01-01

    目的 探讨青年A型行为与儿茶酚胺/核因子kB(NF-icB)/促炎因子通路的关系,为阐明A型行为与心血管疾病关系提供依据.方法 以明尼苏达多相人格调查表2(MMPI-2)A型行为量表评分将900名大一新生(男476人;女424人)分为A型(≥11分,159人)、中间型(6~10分,539人),B型(<5分,202人)3组;采用酶联免疫吸附法检测血清肾上腺素、去甲肾上腺素、白细胞介素(IL)6,IL-18水平.随机在A型,B型、中间型行为者中各抽取8例(男女各4例),抽取各例外周血20 mL,分成5组,分别在5组中加人多巴酚丁胺.,20,30,40和50 umol/L孵育18h后测定各组血清中IL-6和IL-18浓度,然后提取单核细胞用免疫组化法测定NF-KB蛋白表达变化.结果 血清儿茶酚胺浓度与A型行为人格特征呈正相关((r=0.375^0.662,P<0.01);A型组血清肾上腺素、去甲肾上腺(素高于中间型组和B型组;A型行为人格特征与血清IL-6和IL-18浓度呈正相关(r=0.294~0.778,P<0.05或P<0.01).多巴酚丁胺呈剂量依赖性诱导人单核细胞NF-KB/促炎因子通路激活,以40 umol/L多巴酚丁胺为最适宜剂量;40 umol/L多巴酚丁胺诱导激动后,A和B型行为者的单核细胞NF-kB p65及血清IL-6和IL-18均明显上调(P<0.01或P<0.05);A型行为者的单核细胞NF-tcB p65及血清IL-6和IL-18均高于B型行为(P<0.01).结论 A型行为者非应激与应激时借助血清中较高浓度的儿茶酚胺诱导NF-kB/促炎因子通路持续处于激活状态,这可能是青年A型行为者的一个病理生理学特征.%Objective Nuclear factor-KB (NF-kB) and pro-inflammatory cytokines play an important role in initiation and progression of atherosclerosis and coronary disease, type A behavior pattern (TABP) is lifestyle risk factor.The aim of the study was to investigate the association between TABP and activity of/NF-kB/pro-inflammatory cytokines signaling in young persons, and to explore the possible role of catecholamine in inducing activation

  13. 11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes

    International Nuclear Information System (INIS)

    Highlights: •We investigate the role of 11β-HSD1 in skin inflammation. •Various stimuli increase expression of 11β-HSD1 in keratinocytes. •11β-HSD1 knockdown by siRNA decreases cortisol levels in media. •11β-HSD1 knockdown abrogates the response to pro-inflammatory cytokines. •Low-dose versus high-dose cortisol has opposing effects on keratinocyte inflammation. -- Abstract: The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactive cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10−13 M cortisol, whereas 1 × 10−5 M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol concentrations

  14. Antimicrobial activities of squalamine mimics.

    Science.gov (United States)

    Kikuchi, K; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-07-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and fungi. Some had little or no hemolytic activity. The hydrophobicity of the sterol backbone and the length and the cationic charge of the side chains appeared to be critical determinants of activity. One of the squalamine mimics, SM-7, was bactericidal against Escherichia coli, Pseudomonas aeruginosa, and S. aureus; its activity was decreased by divalent or monovalent cations and by bovine serum albumin. Subinhibitory concentrations of SM-7 markedly enhanced the antimicrobial activity of rifampin against gram-negative rods. These results suggest that the compounds may disrupt an outer membrane of gram-negative rods. Squalamine mimics are a new class of broad-spectrum antimicrobial agents. The antagonism of their activity by serum and albumin and their hemolytic properties may limit their use as systemic agents. The squalamine mimics, because of their potencies, broad spectra of antimicrobial activity, and potential for systemic toxicity, appear to be good candidates for development as topical antimicrobial agents. PMID:9210661

  15. Functional analysis of Pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Schneider Ulf C

    2012-02-01

    Full Text Available Abstract Background To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH in vivo and in vitro. Methods The cerebrospinal fluid (CSF of 10 patients suffering from SAH was applied to the transparent skinfold chamber model in male NMRI mice which allows for in vivo analysis of the microcirculatory response to a superfusat. Microvascular diameter changes were quantified and the numbers of rolling and sticking leukocytes were documented using intravital multifluorescence imaging techniques. Furthermore, the pro-inflammatory properties of CSF were assessed in vitro using a monocyte transendothelial migration assay. Results CSF superfusion started to induce significant vasoconstriction on days 4 and 6 after SAH. In parallel, CSF superfusion induced a microvascular leukocyte recruitment, with a significant number of leukocytes rolling (day 6 and sticking (days 2-4 to the endothelium. CSF of patients presenting with cerebral edema induced breakdown of blood vessel integrity in our assay as evidenced by fluorescent marker extravasation. In accordance with leukocyte activation in vivo, significantly higher in vitro monocyte migration rates were found after SAH. Conclusion We functionally characterized inflammatory and vasoactive properties of patients' CSF after SAH in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH.

  16. Phototherapy-treated apoptotic tumor cells induce pro-inflammatory cytokines production in macrophage

    Science.gov (United States)

    Lu, Cuixia; Wei, Yanchun; Xing, Da

    2014-09-01

    Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high fluence low-power laser irradiation (HF-LPLI) induces mitochondrial superoxide anion burst, resulting in oxidative damage to tumor cells. In this study, we further explored the immunological effects of HF-LPLI-induced apoptotic tumor cells. When macrophages were co-incubated with apoptotic cells induced by HF-LPLI, we observed the increased levels of TNF-α secretion and NO production in macrophages. Further experiments showed that NF-κB was activated in macrophages after co-incubation with HF-LPLI-induced apoptotic cells, and inhibition of NF-κB activity by pyrrolidinedithiocarbamic acid (PDTC) reduced the elevated levels of TNF-α secretion and NO production. These data indicate that HF-LPLI-induced apoptotic tumor cells induce the secretion of pro-inflammatory cytokines in macrophages, which may be helpful for better understanding the biological effects of cancer phototherapy.

  17. IL-36α exerts pro-inflammatory effects in the lungs of mice.

    Directory of Open Access Journals (Sweden)

    Ravisankar A Ramadas

    Full Text Available Interleukin (IL- 36 cytokines (previously designated as novel IL-1 family member cytokines; IL-1F5- IL-1F10 constitute a novel cluster of cytokines structurally and functionally similar to members of the IL-1 cytokine cluster. The effects of IL-36 cytokines in inflammatory lung disorders remains poorly understood. The current study sought to investigate the effects of IL-36α (IL-1F6 and test the hypothesis that IL-36α acts as a pro-inflammatory cytokine in the lung in vivo. Intratracheal instillation of recombinant mouse IL-36α induced neutrophil influx in the lungs of wild-type C57BL/6 mice and IL-1αβ(-/- mice in vivo. IL-36α induced neutrophil influx was also associated with increased mRNA expression of neutrophil-specific chemokines CXCL1 and CXCL2 in the lungs of C57BL/6 and IL-1αβ(-/- mice in vivo. In addition, intratracheal instillation of IL-36α enhanced mRNA expression of its receptor IL-36R in the lungs of C57BL/6 as well as IL-1αβ(-/- mice in vivo. Furthermore, in vitro incubation of CD11c(+ cells with IL-36α resulted in the generation of neutrophil-specific chemokines CXCL1, CXCL2 as well as TNFα. IL-36α increased the expression of the co-stimulatory molecule CD40 and enhanced the ability of CD11c(+ cells to induce CD4(+ T cell proliferation in vitro. Furthermore, stimulation with IL-36α activated NF-κB in a mouse macrophage cell line. These results demonstrate that IL-36α acts as a pro-inflammatory cytokine in the lung without the contribution of IL-1α and IL-1β. The current study describes the pro-inflammatory effects of IL-36α in the lung, demonstrates the functional redundancy of IL-36α with other agonist cytokines in the IL-1 and IL-36 cytokine cluster, and suggests that therapeutic targeting of IL-36 cytokines could be beneficial in inflammatory lung diseases.

  18. Neuroprotective effects of activated protein C on intrauterine inflammation-induced neonatal white matter injury are associated with the downregulation of fibrinogen-like protein 2/fibroleukin prothrombinase and the inhibition of pro-inflammatory cytokine expression

    OpenAIRE

    JIN, SHENG-JUAN; Yan LIU; DENG, SHI-HUA; LIAO, LI-HONG; LIN, TU-LIAN; Ning, Qin; LUO, XIAO-PING

    2015-01-01

    Maternal intrauterine inflammation or infection is an important risk factor for neonatal cerebral white matter injury (WMI) and future neurological deficits. Activated protein C (APC), a natural anticoagulant, has been shown to exhibit anti-inflammatory, anti-apoptotic, profibrinolytic and cytoprotective activities. Recent studies have demonstrated that the novel prothrombinase, fibrinogen-like protein 2 (fgl2), contributes to the pathogenesis of a number of inflammatory diseases through the ...

  19. Antimicrobial activity of Securidaca longipedunculata.

    Science.gov (United States)

    Ajali, U; Chukwurah, B K C

    2004-11-01

    The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods. PMID:15636189

  20. REDUCED TISSUE OSMOLARITY INCREASES TRPV4 EXPRESSION AND PRO-INFLAMMATORY CYTOKINES IN INTERVERTEBRAL DISC CELLS

    Science.gov (United States)

    Walter, B.A.; Purmessur, D; Moon, A.; Occhiogrosso, J.; Laudier, D.M.; Hecht, A.C.; Iatridis, J.C.

    2016-01-01

    The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs) and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4) ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα) regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β) and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease. PMID:27434269

  1. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  2. Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride.

    Science.gov (United States)

    Tian, Yuhu; Huo, Meijun; Li, Guangsheng; Li, Yanyan; Wang, Jundong

    2016-10-01

    F toxicity to immune system, especially to macrophage, has been studied a lot recently. Nuclear factor-kappa B (NF-κB), as a transcription factor, plays a central role in immune and inflammatory responses via the regulation of downstream gene expression. Recent studies indicated that fluoride effect on inflammatory cytokine secretion, however, the molecular mechanism was less understood. In our study, peritoneal macrophages (PMs) were divided several groups and were administrated sodium fluoride (NaF, 50, 100, 200, 400, 800 μM) and/or lipopolysaccharide (LPS, 30 ng/mg). The mRNA expression of p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in macrophages exposed to fluoride was determined by quantitative real-time RT-PCR respectively. The translocation of NF-κB from cytoplasm to nucleus, which in a way reflects NF-κB activity, was demonstrated by Immunofluorescence and ELISA. Our results showed that fluoride had a dose-dependent effect on NF-κB activity, which coincided with LPS-induced mRNA expression of its downstream genes, iNOS and IL-1β. Fluoride alone causes no effect on gene expression. However, the mRNA expression of TNF-α showed non-NF-κB-dependent manner. Therefore, we come to the conclusion that fluoride can regulate LPS-induced mRNA expression of iNOS and IL-1β via NF-κB pathway in mouse peritoneal macrophages. PMID:27421105

  3. Macrophage elastase (MMP-12: a pro-inflammatory mediator?

    Directory of Open Access Journals (Sweden)

    Soazig Nénan

    2005-03-01

    Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

  4. Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC

    NARCIS (Netherlands)

    Heida, F. H.; Hulscher, J. B. F.; Schurink, M.; van Vliet, M. J.; Kooi, E. M. W.; Kasper, D. C.; Pones, M.; Bos, A. F.; Benkoe, T. M.

    2015-01-01

    Introduction: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC developm

  5. Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC

    NARCIS (Netherlands)

    Heida, F.H.; Hulscher, J.B.; Schurink, M.; Vliet, M.J. van; Kooi, E.M.; Kasper, D.C.; Pones, M.; Bos, A.F; Benkoe, T.M.

    2015-01-01

    INTRODUCTION: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC developm

  6. Iodinated contrast media alter immune responses in pro-inflammatory states.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

  7. Downregulation of pro-inflammatory mediators by a water extract of Schisandra chinensis (Turcz.) Baill fruit in lipopolysaccharide-stimulated RAW 264.7 macrophage cells.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang-Hee; Lee, Seungheon; Park, Sang Rul; Jeong, Jin-Woo; Choi, Yung Hyun; Seo, Yong Taek; Jang, Young Pyo; Kim, Gi-Young

    2013-09-01

    Schisandra chinensis has a long-standing history of medicinal use as a tonic, a sedative, an anti-tussive, and an anti-aging drug. Nevertheless, the antagonistic effects of S. chinensis against lipopolysaccharide (LPS)-stimulated responses have not yet been studied. In this study, we investigated whether water extract of S. chinensis fruit (WESC) has the ability to attenuate the expression of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophage cells. WESC inhibited the expression of LPS-induced pro-inflammatory mediators, namely, NO, PGE2, and TNF-α. Furthermore, gene expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α was inhibited both at mRNA and protein synthesis levels, without any cytotoxic effect. Moreover, WESC significantly suppressed LPS-induced DNA-binding activity of NF-κB by inhibiting degradation of IκBα. It was found that pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulates the expression of these pro-inflammatory genes to be closely regulated by NF-κB activity. Furthermore, we found that WESC retains dephosphorylation of Akt in response to LPS, and consequently suppressed the DNA-binding activity of NF-κB in RAW 264.7 macrophage cells. LY294002, a specific Akt inhibitor, attenuated LPS-induced pro-inflammatory gene expression via suppression of NF-κB activity. Taken together, our results indicate that WESC downregulates the expression of pro-inflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-stimulated RAW 264.7 macrophage cells by suppressing Akt-dependent NF-κB activity.

  8. Schizophrenia patients with a history of childhood trauma have a pro-inflammatory phenotype

    OpenAIRE

    Dennison, Una; McKernan, Declan P.; Cryan, John F; Dinan, Timothy G.

    2012-01-01

    Background. Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls. Method. We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma ...

  9. Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.

    Science.gov (United States)

    Frank, Matthew G; Hershman, Sarah A; Weber, Michael D; Watkins, Linda R; Maier, Steven F

    2014-02-01

    Chronic stress as well as chronic treatment with glucocorticoids (GCs) primes the neuroinflammatory response to a subsequent pro-inflammatory challenge. However, it remains unclear whether chronic GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. In the present set of studies, male Sprague-Dawley rats underwent sham surgery or were adrenalectomized and then treated with varying concentrations of corticosterone (CORT; 0, 25, 50, and 75 μg/ml) administered in their drinking water. After 10 days of CORT exposure, whole hippocampus was collected and expression of glial activation markers measured or hippocampal microglia were isolated and challenged with LPS to probe for CORT-induced sensitization of pro-inflammatory responses. Chronic CORT exposure increased the gene expression of NLRP3, Iba-1, MHCII, and NF-κBIα in a concentration dependent manner. Chronic CORT (75 μg/ml) exposure potentiated the microglial proinflammatory response (TNFα, IL-1β, IL-6 and NLRP3) to LPS compared to the microglial response of sham surgery animals treated with vehicle. The present set of results demonstrate that chronic exposure to GCs primes microglia to pro-inflammatory stimuli and add to a growing body of evidence suggesting that a permissive function of GCs is that of an endogenous danger signal or alarmin.

  10. Apigenin inhibits PMA-induced expression of pro-inflammatory cytokines and AP-1 factors in A549 cells.

    Science.gov (United States)

    Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Ramesh, Govindarajan T; Chidananda Sharma, S

    2015-05-01

    Acute and chronic alveolar or bronchial inflammation is thought to be central to the pathogenesis of many respiratory disorders. Cytokines and granulocyte macrophage colony-stimulating factors (GM-CSF) play an important role in chronic inflammation. Activator protein-1 (AP-1) the superfamily of transcription factors is involved in proliferation, differentiation, apoptosis, and transformation including inflammation. Understanding the function and regulation of proinflammatory factors involved in inflammation may provide the novel therapeutic strategies in the treatment of inflammatory diseases. Our aim of the present study is to investigate the pro-inflammatory cytokines and pattern of AP-1 factors expressed during activation of lung adenocarcinoma A549 cells by Phorbol-12-myristate-13-acetate (PMA) and to understand the anti-inflammatory effect of apigenin. A549 cells were treated with and without PMA or apigenin, and the cell viability was assessed by MTT assay. Expressions of inflammatory mediators and different AP-1 factors were analyzed by semi-quantitative RT-PCR. IL-6 protein secreted was analyzed by ELISA, and expressions of IL-1β, c-Jun, and c-Fos proteins were analyzed by Western blotting. Activation of A549 cells by PMA, induced the expression of pro-inflammatory cytokine (IL-1β, IL-2, IL-6, IL-8, and TNF-α) mRNAs and secretion of IL-6 and the expression of specific AP-1 factors (c-Jun, c-Fos, and Fra-1). Treatment of cells with apigenin, significantly inhibited PMA-stimulated mRNA expression of above pro-inflammatory cytokines, AP-1 factors, cyclooxygenase-2, and secretion of IL-6 protein. Results suggested that the AP-1 factors may be involved in inflammation and apigenin has anti-inflammatory effect, which may be useful for therapeutic management of lung inflammatory diseases. PMID:25666088

  11. Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients

    Directory of Open Access Journals (Sweden)

    Calabuig Miguel

    2008-11-01

    Full Text Available Abstract Background Coeliac disease (CD is an enteropathy characterized by an aberrant immune response to cereal-gluten proteins. Although gluten peptides and microorganisms activate similar pro-inflammatory pathways, the role the intestinal microbiota may play in this disorder is unknown. The purpose of this study was to assess whether the faecal microbiota of coeliac patients could contribute to the pro-inflammatory milieu characteristic of CD and the possible benefits of bifidobacteria. Methods The effect of faeces of 26 CD patients with active disease (mean age 5.5 years, range 2.1–12.0 years, 18 symptom-free coeliac disease (SFCD patients (mean age 5.5 years, range 1.0–12.3 years on a gluten-free diet for 1–2 years; and 20 healthy children (mean age 5.3 years, range 1.8–10.8 years on induction of cytokine production and surface antigen expression in peripheral blood mononuclear cells (PBMCs were determined. The possible regulatory roles of Bifidobacterium longum ES1 and B. bifidum ES2 co-incubated with faecal samples were also assessed in vitro. Results Faeces of both active CD and SFCD patients, representing an imbalanced microbiota, significantly increased TNF-α production and CD86 expression in PBMCs, while decreased IL-10 cytokine production and CD4 expression compared with control samples. Active CD-patient samples also induced significantly higher IFN-γ production compared with controls. However, Bifidobacterium strains suppressed the pro-inflammatory cytokine pattern induced by the large intestinal content of CD patients and increased IL-10 production. Cytokine effects induced by faecal microbiota seemed to be mediated by the NFκB pathway. Conclusion The intestinal microbiota of CD patients could contribute to the Th1 pro-inflammatory milieu characteristic of the disease, while B. longum ES1 and B. bifidum ES2 could reverse these deleterious effects. These findings hold future perspectives of interest in CD therapy.

  12. Antimicrobial activities of squalamine mimics.

    OpenAIRE

    Kikuchi, K.; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-01-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphyl...

  13. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP.

    Directory of Open Access Journals (Sweden)

    Kishore V L Parsa

    2006-07-01

    Full Text Available Francisella tularensis, a Gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. Macrophage responses to F. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (IL-12, which is critical for immunity against infection. Molecular mechanisms regulating production of these inflammatory mediators are poorly understood. Herein we report that the SH2 domain-containing inositol phosphatase (SHIP is phosphorylated upon infection of primary murine macrophages with the genetically related F. novicida, and negatively regulates F. novicida-induced cytokine production. Analyses of the molecular details revealed that in addition to activating the MAP kinases, F. novicida infection also activated the phosphatidylinositol 3-kinase (PI3K/Akt pathway in these cells. Interestingly, SHIP-deficient macrophages displayed enhanced Akt activation upon F. novicida infection, suggesting elevated PI3K-dependent activation pathways in absence of SHIP. Inhibition of PI3K/Akt resulted in suppression of F. novicida-induced cytokine production through the inhibition of NFkappaB. Consistently, macrophages lacking SHIP displayed enhanced NFkappaB-driven gene transcription, whereas overexpression of SHIP led to decreased NFkappaB activation. Thus, we propose that SHIP negatively regulates F. novicida-induced inflammatory cytokine response by antagonizing the PI3K/Akt pathway and suppressing NFkappaB-mediated gene transcription. A detailed analysis of phosphoinositide signaling may provide valuable clues for better understanding the pathogenesis of tularemia.

  14. TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Griffiths Gareth

    2009-07-01

    Full Text Available Abstract Background Phosphatidylcholine (PC is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. Methods PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs. Results The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs. Conclusion PC

  15. Pro-inflammatory cytokines and nitric oxide inhibitory constituents from Cassia occidentalis roots.

    Science.gov (United States)

    Patel, Neeraj K; Pulipaka, Sravani; Dubey, Shashi P; Bhutani, Kamlesh K

    2014-05-01

    The anti-inflammatory and cytotoxic activity of thirty-six extracts of nine Indian medicinal plants were determined by measuring the inhibition of production of nitric oxide (NO), interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Their cytotoxic activity against macrophages was determined by MTT assay. The ethyl acetate (EtOAc) extract of Cassia occidentalis L. (roots) (IC50 = 21.3 to 43.1 microg/mL) and Mimosa pudica (whole plant) (1C50= 31.7 to 47.2 microg/mL) and the dichloromethane (DCM) extract of Leucas cephalotes (whole plant) (IC50 = 46.8 to 49.3 microg/mL) exhibited significant anti-inflammatory activity by in vitro inhibition of the production of TNF-alpha, IL-1beta and NO in LPS stimulated RAW 264.7 cells. Furthermore, the five compounds isolated from the ethyl acetate extract of Cassia occidentalis roots were found to suppress LPS-induced IL-1beta, TNF-alpha and NO production in a concentration-dependent manner in these cells at 1C50 values ranging from 22.5 to 97.4 microM. Emodin and chrysophanol were also found active in inhibiting pro-inflammatory cytokines in vivo. These findings justify an ethnopharmacological use of C occidentalis roots as an effective herbal remedy for the treatment and prevention of inflammation and associated ailments.

  16. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Mounira Sabilallah

    Full Text Available Kainic acid (KA is routinely used to elicit status epilepticus (SE and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%. Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1 and anti-inflammatory (M2 genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered.

  17. Total body fat, pro-inflammatory cytokines and insulin resistance in Indian subjects

    International Nuclear Information System (INIS)

    There is a growing epidemic of insulin resistance syndrome (IRS) in Indians. We postulate that increased susceptibility of the urban Indians to insulin resistance is a result of a tendency to increased fat deposition from the time of intrauterine life (thrifty phenotype), exaggerated in the urban environment by a positive energy balance. The pro-inflammatory cytokines secreted by the inflammatory cells as well by the adipose tissue could aggravate insulin resistance and endothelial damage and therefore, increase the susceptibility to type 2 diabetes and coronary heart disease (CHD) independent of the previously proposed glucose fatty acid cycle mechanism. In a preliminary study, we propose to make detailed measurements of the proposed mechanisms in a selected population from 3 geographical locations in and near the city of Pune, India and also validate simple 'epidemiologic' measurements of body composition with 'reference' measurements. One hundred men (30 to 50y) each from the three geographical locations (rural, urban slum-dwellers and urban middle class in Pune) will be studied for: (i) Body composition: Anthropometric and bioimpedance measurement of total body fat (to be calibrated against deuterated water in 30 subjects from each location), and muscle mass by anthropometry and urinary creatinine excretion; (ii) Body fat distribution by subscapular- triceps ratio, waist-hip ratio; (iii) Metabolic: Glucose tolerance and insulin resistance variables (insulin, lipids, NEFA) and leptin; (iv) Endothelial markers: e-Selectin and von Willebrand Factor (vWF); (v) Inflammatory markers and pro-inflammatory cytokines: C-reactive protein (CRP), Interleukin-6 (IL-6) and tumour necrosis factor (TNF- α); (vi) Energy Balance: Assessment of nutritional intake (calories, carbohydrates, proteins and fats, n3 and n6 fatty acids) and physical activity by a questionnaire. Insulin resistance variables, endothelial markers, cytokines and obesity parameters will be compared in the 3

  18. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood.

    Science.gov (United States)

    Chen, E; Miller, G E; Kobor, M S; Cole, S W

    2011-07-01

    The notion that family support may buffer individuals under adversity from poor outcomes has been theorized to have important implications for mental and physical health, but little is known about the biological mechanisms that explain these links. We hypothesized that adults who grew up in low socioeconomic status (SES) households but who experienced high levels of maternal warmth would be protected from the pro-inflammatory states typically associated with low SES. A total of 53 healthy adults (aged 25-40 years) low in SES early in life were assessed on markers of immune activation and systemic inflammation. Genome-wide transcriptional profiling also was conducted. Low early-life SES individuals who had mothers, who expressed high warmth toward them, exhibited less Toll-like receptor-stimulated production of interleukin 6, and reduced bioinformatic indications of pro-inflammatory transcription factor activity (NF-κB) and immune activating transcription factor activity (AP-1) compared to those who were low in SES early in life but experienced low maternal warmth. To the extent that such effects are causal, they suggest the possibility that the detrimental immunologic effects of low early-life SES environments may be partly diminished through supportive family climates.

  19. Antimicrobial activity of benzylisoquinoline alkaloids.

    Science.gov (United States)

    Villar, A; Mares, M; Rios, J L; Canton, E; Gobernado, M

    1987-04-01

    The antimicrobial in vitro activity of 14 benzylisoquinoline alkaloids was investigated by agar diffusion and agar dilution methods against several genera of microorganisms that included Streptococcus, Staphylococcus, Bacillus, Lysteria, Escherichia, Salmonella, Klebsiella, Pseudomonas, Enterobacter, Serratia, Shigella, Mycobacterium and Candida. Anolobine was the most active compound against grampositive bacteria with MIC90 between 12 and 50 mg/l; less active were anonaine, lysicamine and liriodenine. All the alkaloids of the noraporphine and oxoaporphine groups, with the exception of isopiline, showed activity against Mycobacterium phlei (MIC 6-25 mg/l). Candida albicans ATCC26555 was inhibited by anonaine, nornantenine and xylopine (MIC 3-12 mg/l). None of the alkaloids tested had a significant activity against gramnegative rods. The action against susceptible microorganisms was bactericidal. PMID:3615557

  20. Antimicrobial activity of Argemone ochroleuca Sweet (Chicalote)

    OpenAIRE

    Francisco Daniel REYES; Celia Jimena PEÑA; Canales, Margarita; Jiménez, Manuel; Samuel MERÁZ; Tzasna HERNANDEZ

    2011-01-01

    Argemone ochroleuca Sweet (Papaveraceae) is used to treat eye infection, respiratory and dermatological disorders in Tepotzotlán, State of México (México). The aim of this work was to investigate antimicrobial activity of hexane, ethyl acetate and methanol extracts from aerial parts of A. ochroleuca. The antimicrobial activity was evaluated against thirteen bacteria and nine fungal strains. Only methanol extract showed antimicrobial activity. S. aureus (MIC= 125 ¿g/mL) and C. neoformans (MIC=...

  1. Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages

    Directory of Open Access Journals (Sweden)

    Masoumeh Tangestani Fard

    2015-01-01

    Full Text Available Introduction: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a widely grown plant in most tropical countries and it has been recognized traditionally for several medicinal benefits. Objectives: The objective of this study was to investigate the anti-inflammatory properties of M. oleifera extract on lipopolysaccharide (LPS - stimulated macrophages. Materials and Methods: The anti-inflammatory effect of M. oleifera hydroethanolic bioactive leaves extracts was evaluated by assessing the inhibition of nitric oxide (NO production during Griess reaction and the expression of pro-inflammatory mediators in macrophages. Results: Interestingly, we found that M. oleifera hydroethanolic bioactive leaves extract significantly inhibited the secretion of NO production and other inflammatory markers such as prostaglandin E 2 , tumor necrosis factor alpha, interleukin (IL-6, and IL-1b. Meanwhile, the bioactive extract has induced the production of IL-10 in a dose-dependent manner. In addition, M. oleifera hydroethanolic bioactive leaves extract effectively suppressed the protein expression of inflammatory markers inducible NO synthase, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B-cells p65 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. Conclusion: These findings support the traditional use of M. oleifera plant as an effective treatment for inflammation associated diseases/disorders.

  2. Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

    OpenAIRE

    Daeian, Nesa; Radfar, Mania; Jahangard-Rafsanjani, Zahra; Hadjibabaie, Molouk; Ghavamzadeh, Ardeshir

    2014-01-01

    Background Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. Findings Plasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, p...

  3. Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells.

    Science.gov (United States)

    Alayli, Farah; Scholle, Frank

    2016-09-01

    Dengue virus (DV) has become the most prevalent arthropod borne virus due to globalization and climate change. It targets dendritic cells during infection and leads to production of pro-inflammatory cytokines and chemokines. Several DV non-structural proteins (NS) modulate activation of human dendritic cells. We investigated the effect of DV NS1 on human monocyte-derived dendritic cells (mo-DCs) during dengue infection. NS1 is secreted into the serum of infected individuals where it interacts with various immune mediators and cell types. We purified secreted DV1 NS1 from supernatants of 293T cells that over-express the protein. Upon incubation with mo-DCs, we observed NS1 uptake and enhancement of early DV1 replication. As a consequence, mo-DCs that were pre-exposed to NS1 produced more pro-inflammatory cytokines in response to subsequent DV infection compared to DCs exposed to heat-inactivated NS1 (HNS1). Therefore the presence of exogenous NS1 is able to modulate dengue infection in mo-DCs. PMID:27348054

  4. Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.

    Science.gov (United States)

    Garza-Cuartero, L; O'Sullivan, J; Blanco, A; McNair, J; Welsh, M; Flynn, R J; Williams, D; Diggle, P; Cassidy, J; Mulcahy, G

    2016-07-01

    Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has an annual incidence in cattle of 0.5% in the Republic of Ireland and 4.7% in the UK, despite long-standing eradication programmes being in place. Failure to achieve complete eradication is multifactorial, but the limitations of diagnostic tests are significant complicating factors. Previously, we have demonstrated that Fasciola hepatica infection, highly prevalent in these areas, induced reduced sensitivity of the standard diagnostic tests for BTB in animals co-infected with F. hepatica and M. bovis. This was accompanied by a reduced M. bovis-specific Th1 immune response. We hypothesized that these changes in co-infected animals would be accompanied by enhanced growth of M. bovis. However, we show here that mycobacterial burden in cattle is reduced in animals co-infected with F. hepatica. Furthermore, we demonstrate a lower mycobacterial recovery and uptake in blood monocyte-derived macrophages (MDM) from F. hepatica-infected cattle which is associated with suppression of pro-inflammatory cytokines and a switch to alternative activation of macrophages. However, the cell surface expression of TLR2 and CD14 in MDM from F. hepatica-infected cattle is increased. These findings reflecting the bystander effect of helminth-induced downregulation of pro-inflammatory responses provide insights to understand host-pathogen interactions in co-infection.

  5. Antimicrobial activities of Barringtonia acutangula.

    Science.gov (United States)

    Rahman, M Mukhlesur; Polfreman, David; MacGeachan, Jodie; Gray, Alexander I

    2005-06-01

    Crude extracts and VLC fractions from the stem bark of Barringtonia acutangula (L.) Gaertn (Fam. Lecythidaceae) were screened for their antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria and two fungi using a microdilution titre assay. Among the crude extracts, petroleum ether extract showed good activity against all test organisms. The VLC fraction PE 16 was found to be very effective against Bacillus subtilis (MIC=25 microg/ml) and Aspergillus niger (MIC=12.5 microg/ml). The activities were compared to standard antibiotics-kanamycin and fluconazole. The major compound from PE16 was identified as 12, 20(29)-lupadien-3-ol by NMR spectroscopy. PMID:16114086

  6. PAMPs and DAMPs stimulate the expression of pro-inflammatory cytokines in vitro in a fibroblast cell-line from rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Ossum, C.G.; Nielsen, Michael Engelbrecht

    activates downstream signalling pathways, which subsequently leads to expression of pro-inflammatory cytokines and chemokines. DAMPs released from necrotic cells may also bind to and activate similar downstream signalling events. In telosts was found that mechanical damage of the muscle tissue using sterile...... needles induced a very rapid expression of the pro-inflammatory cytokines IL-1β, IL-8 and IL-10 as measured by real-time PCR. The results imply that cells located in the muscular tissue in addition to recruited cells are involved in the observed increased cytokine / chemokine expression. It is believed....... The present study reinforce the idea that fibroblasts are able to react to PAMPs and DAMPs and that non-immune cell-types play an important role in the inflammatory reaction per se. From an evolutionary perspective the facilitation of an inflammatory response through recognition of PAMPs and DAMPs by non...

  7. Treg cells expressing the co-inhibitory molecule TIGIT selectively inhibit pro-inflammatory Th1 and Th17 cell responses

    OpenAIRE

    Joller, Nicole; Lozano, Ester; Burkett, Patrick R.; Patel, Bonny; Xiao, Sheng; Zhu, Chen; Xia, Junrong; Tan, Tze G.; Sefik, Esen; Yajnik, Vijay; Sharpe, Arlene H.; Quintana, Francisco J.; Mathis, Diane; Benoist, Christophe; Hafler, David A.

    2014-01-01

    Foxp3+ T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3+ T cells expressing the co-inhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses pro-inflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT+ Treg cells as an activated Treg subse...

  8. The amelioration of phagocytic ability in microglial cells by curcumin through the inhibition of EMF-induced pro-inflammatory responses

    OpenAIRE

    He, Gen-Lin; Liu, Yong; Min LI; Chen, Chun-Hai; Gao, Peng; Yu, Zheng-Ping; Yang, Xue-Sen

    2014-01-01

    Background Insufficient clearance by microglial cells, prevalent in several neurological conditions and diseases, is intricately intertwined with MFG-E8 expression and inflammatory responses. Electromagnetic field (EMF) exposure can elicit the pro-inflammatory activation and may also trigger an alteration of the clearance function in microglial cells. Curcumin has important roles in the anti-inflammatory and phagocytic process. Here, we evaluated the ability of curcumin to ameliorate the phag...

  9. Synthesis and antimicrobial activity of squalamine analogue.

    Science.gov (United States)

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  10. Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species.

    Science.gov (United States)

    Rebiger, Lars; Lenzen, Sigurd; Mehmeti, Ilir

    2016-01-21

    Brown adipose tissue (BAT) cells have a very high oxidative capacity. On the other hand, in obesity and obesity-related diabetes, levels of pro-inflammatory cytokines are elevated, which might promote BAT dysfunction and consequently impair carbohydrate metabolism and thereby exacerbate cellular dysfunction and promote diabetes progression. Therefore, the antioxidative enzyme status of a brown adipocyte cell line and its susceptibility towards pro-inflammatory cytokines, which participate in the pathogenesis of diabetes, and reactive oxygen species (ROS) were analysed. Mature brown adipocytes exhibited significantly higher levels of expression of mitochondrially and peroxisomally located antioxidative enzymes compared with non-differentiated brown adipocytes. Pro-inflammatory cytokines induced a significant decrease in the viability of differentiated brown adipocytes, which was accompanied by a massive ROS production and down-regulation of BAT-specific markers, such as uncoupling protein 1 (UCP-1) and β-Klotho. Taken together, the results strongly indicate that pro-inflammatory cytokines cause brown adipocyte dysfunction and death through suppression of BAT-specific proteins, especially of UCP-1 and β-Klotho, and consequently increased oxidative stress.

  11. Retracted: Effects of pro-inflammatory cytokines on mineralization potential of rat dental pulp stem cells

    NARCIS (Netherlands)

    Yang, X.; Walboomers, X.F.; Bian, Z.; Jansen, J.A.; Fan, M.

    2011-01-01

    The following article from the Journal of Tissue Engineering and Regenerative Medicine, 'Effects of Pro-inflammatory Cytokines on Mineralization Potential of Rat Dental Pulp Stem Cells' by Yang X, Walboomers XF, Bian Z, Jansen JA, Fan M, published online on 11 July 2011 in Wiley Online Library (onli

  12. Childhood overweight and asthma symptoms, the role of pro-inflammatory proteins

    NARCIS (Netherlands)

    Bekkers, M. B. M.; Brunekreef, B.; de Jongste, J. C.; Kerkhof, M.; Smit, H. A.; Postma, D. S.; Gehring, U.; Wijga, A. H.

    2012-01-01

    Background Systemic inflammation is suggested as a mechanism by which overweight might induce asthma. However, few studies have linked childhood overweight, inflammation and asthma. Objective To study the association between body mass index (BMI), asthma symptoms and pro-inflammatory proteins. Metho

  13. Modulation of pro-inflammatory cytokines in normal and inflamed skin

    NARCIS (Netherlands)

    A.R. Companjen (Arjen)

    2001-01-01

    textabstractThis thesis describes the expression and modulation of pro-inflammatory cytokines in normal and inflamed skin. During the last few decades it has become clear that the skin comprises a complex network of interacting cells including keratinocytes (KC). dendritic cells (such as Langerhans

  14. PAMPs and DAMPs stimulate the expression of pro-inflammatory cytokines in vitro in fibroblasts from fish

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Ossum, C.G.; Przybylska, Dominika;

    The recognition of PAMPs by immune cells relies on conserved PRRs such as TLRs, NLRs and RLRs leading to activation of NFB signaling pathways. These receptors are activated upon stimulation by different ligands such as bacterial or viral components. The binding of ligands to the receptors...... activates downstream signalling pathways, which subsequently leads to expression of pro-inflammatory cytokines and chemokines. DAMPs released from necrotic cells may also bind to and activate similar downstream signalling events. In teleosts it was found that mechanical damage of the muscle tissue using...... in a significant up-regulation of the expression of IL-1β, IL-8 and IL-10 and stimulation with supernatant from sonicated cells led to a significant up-regulation of IL-1β and IL-10, while debris only stimulated the expression of IL-1β. TLR-2 and -4 are not described from salmonid fishes; however TLR-3, -5 and -9...

  15. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

    Science.gov (United States)

    Zubair, Swaleha; Ajmal, Mohd; Siddiqui, Sheelu Shafiq; Moin, Shagufta; Owais, Mohammad

    2016-01-01

    Background Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease. Methods The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR. Results The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects. Conclusion The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner. PMID:27575603

  16. Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.

    Science.gov (United States)

    Porto, Marilia de Paula; da Silva, Glenda Nicioli; Luperini, Bruno Cesar Ottoboni; Bachiega, Tatiana Fernanda; de Castro Marcondes, João Paulo; Sforcin, José Maurício; Salvadori, Daisy Maria Fávero

    2014-11-01

    Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.

  17. Inhibition of Pro-inflammatory mediators and cytokines by Chlorella Vulgaris extracts

    Directory of Open Access Journals (Sweden)

    G Sibi

    2016-01-01

    Full Text Available Objective: The aim of this study was to determine the in vitro anti-inflammatory activities of solvent fractions from Chlorella vulgaris by inhibiting the production of pro-inflammatory mediators and cytokines. Methods: Methanolic extracts (80% of C. vulgaris were prepared and partitioned with solvents of increasing polarity viz., n-hexane, chloroform, ethanol, and water. Various concentrations of the fractions were tested for cytotoxicity in RAW 264.7 cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay, and the concentrations inducing cell growth inhibition by about 50% (IC50 were chosen for further studies. Lipopolysaccharide (LPS stimulated RAW 264.7 cells were treated with varying concentrations of C. vulgaris fractions and examined for its effects on nitric oxide (NO production by Griess assay. The release of prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α, and interleukin 6 (IL-6 were quantified using enzyme-linked immunosorbent assay using Celecoxib and polymyxin B as positive controls. Results: MTT assay revealed all the solvent fractions that inhibited cell growth in a dose-dependent manner. Of all the extracts, 80% methanolic extract exhibited the strongest anti-inflammatory activity by inhibiting NO production (P < 0.01, PGE2 (P < 0.05, TNF-α, and IL-6 (P < 0.001 release in LPS induced RAW 264.7 cells. Both hexane and chloroform fractions recorded a significant (P < 0.05 and dose-dependent inhibition of LPS induced inflammatory mediators and cytokines in vitro. The anti-inflammatory effect of ethanol and aqueous extracts was not significant in the study. Conclusion: The significant inhibition of inflammatory mediators and cytokines by fractions from C. vulgaris suggests that this microalga would be a potential source of developing anti-inflammatory agents and a good alternate for conventional steroidal and nonsteroidal anti-inflammatory drugs.

  18. Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide.

    Science.gov (United States)

    Ghorbel, Imen; Maktouf, Sameh; Kallel, Choumous; Ellouze Chaabouni, Semia; Boudawara, Tahia; Zeghal, Najiba

    2015-07-01

    The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver.

  19. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    Full Text Available One of the main differences among platelet-rich plasma (PRP products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF and leukocyte-platelet rich plasma (L-PRP scaffolds was determined by enzyme-linked immunosorbent assay (ELISA and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

  20. Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression.

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    Martin Michaelis

    Full Text Available Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549 cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher. Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.

  1. Antimicrobial Activity of Drosera rotundifolia L.

    Directory of Open Access Journals (Sweden)

    Miroslava Kačániová

    2014-11-01

    Full Text Available Droseracae spp. is widely used in folk medicine. In the present study, the antimicrobial activities of the four Drosera rotundifolia L. (D8.11, D15.12, 18.10, 8.11 samples were investigated. The antimicrobial activities were determined by using agar disc diffusion method against grampositive bacteria (Bacillus thurigiensis, Staphylococcus aureus, Listeria monocytogenes and gramnegative bacteria (Yersinia enterocolitica, Salmonella enteritidis.  The results of the disk diffusion method showed very different activity against all tested strains of microorganisms. The best antimicrobial activity of ethanolic extract Drosera rotundifolia L. against Salmonella enteritidis was found at Drosera rotundifolia (D8.11.

  2. Apoptosis and pro-inflammatory cytokine response of mast cells induced by influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available The pathogenesis of the influenza A virus has been investigated heavily, and both the inflammatory response and apoptosis have been found to have a definitive role in this process. The results of studies performed by the present and other groups have indicated that mast cells may play a role in the severity of the disease. To further investigate cellular responses to influenza A virus infection, apoptosis and inflammatory response were studied in mouse mastocytoma cell line P815. This is the first study to demonstrate that H1N1 (A/WSN/33, H5N1 (A/Chicken/Henan/1/04, and H7N2 (A/Chicken/Hebei/2/02 influenza viruses can induce mast cell apoptosis. They were found to do this mainly through the mitochondria/cytochrome c-mediated intrinsic pathway, and the activation of caspase 8-mediated extrinsic pathway was here found to be weak. Two pro-apoptotic Bcl-2 homology domain 3 (BH3 -only molecules Bim and Puma appeared to be involved in the apoptotic pathways. When virus-induced apoptosis was inhibited in P815 cells using pan-caspase (Z-VAD-fmk and caspase-9 (Z-LEHD-fmk inhibitors, the replication of these three subtypes of viruses was suppressed and the secretions of pro-inflammatory cytokines and chemokines, including IL-6, IL-18, TNF-α, and MCP-1, decreased. The results of this study may further understanding of the role of mast cells in host defense and pathogenesis of influenza virus. They may also facilitate the development of novel therapeutic aids against influenza virus infection.

  3. Antimicrobial activity of Aspilia latissima (Asteraceae)

    OpenAIRE

    Souza, Jeana M.E.; Chang, Marilene R.; Brito, Daniela Z.; Katyuce S. Farias; Damasceno-Junior, Geraldo A.; Izabel C.C. Turatti; Norberto P. Lopes; Santos, Edson A.; Carollo, Carlos A.

    2015-01-01

    Abstract We evaluated the antimicrobial activity of Aspilia latissima - an abundant plant from the Brazilian Pantanal region - against Candida albicans, Candida parapsilosis, Candida krusei, Candida tropicalis, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli and Staphylococcus aureus. The crude extracts and fractions showed activity in all tested microorganisms. The chloroform fraction of the leaves and roots showed the most antimicrobial activity against S. aureus, with an MI...

  4. Antimicrobial activity of some Iranian medicinal plants

    Directory of Open Access Journals (Sweden)

    Ghasemi Pirbalouti Abdollah

    2010-01-01

    Full Text Available The major aim of this study was to determine the antimicrobial activity of the extracts of eight plant species which are endemic in Iran. The antimicrobial activities of the extracts of eight Iranian traditional plants, including Hypericum scabrum, Myrtus communis, Pistachia atlantica, Arnebia euchroma, Salvia hydrangea, Satureja bachtiarica, Thymus daenensis and Kelussia odoratissima, were investigated against Escherichia coli O157:H7, Bacillus cereus, Listeria monocytogenes and Candida albicans by agar disc diffusion and serial dilution assays. Most of the extracts showed a relatively high antimicrobial activity against all the tested bacteria and fungi. Of the plants studied, the most active extracts were those obtained from the essential oils of M. communis and T. daenensis. The MIC values for active extract and essential oil ranged between 0.039 and 10 mg/ml. It can be said that the extract and essential oil of some medicinal plants could be used as natural antimicrobial agents in food preservation. .

  5. Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus.

    Science.gov (United States)

    Vinet, Jonathan; Vainchtein, Ilia D; Spano, Carlotta; Giordano, Carmela; Bordini, Domenico; Curia, Giulia; Dominici, Massimo; Boddeke, Hendrikus W G M; Eggen, Bart J L; Biagini, Giuseppe

    2016-08-01

    Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS-based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine-treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen-presenting cell phenotype correlated with the presence of CD4(pos) T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL-1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL-1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)-9 and 12 while microglia only expressed MMP-12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350-1362. PMID:27246930

  6. ANTIMICROBIAL ACTIVITY OF LACTIC ACID BACTERIAL ISOLATES

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    Utkarsha S. Shivsharan

    2013-08-01

    Full Text Available Micro-organisms have tendency to produce antimicrobial substances which show biological activity against other kind of micro-organisms. This phenomenon of bacterial antagonism is observed in lactic acid bacteria with competitive advantages. The lactic acid bacteria are commonly present in many fermented products, fruits and milk products. The variety of antimicrobial substances produced by lactic acid bacteria showing good inhibition capacity include production of lactic acid, acetic acid, hydrogen peroxide, carbon dioxide, diacetyl and bacteriocin. Bacteriocins produced by lactic acid bacteria are the subject of intense research because of their antimicrobial activity against food born bacteria such as Listeria monocytogenes, staphylococcus aureus, Bacillus cereus, Clostridium botulinum and several others .Bacteriocins may be bacteriostatic or bactericidal with narrow or broad range of activity. The main of the study was to study the antimicrobial activity of such lactic acid bacterial isolates.

  7. FUNDAMENTAL IMMUNOBIOLOGY OF PRO-INFLAMMATORY CYTOKINES AND MIF

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    A. P. Suslov

    2006-01-01

    Full Text Available Fundamental immunobiology of proinflammatory cytokines and MIFThere are a lot of similarity as well as differences when we compare cytokines with MIF according their biological properties. MIF characteristics are unique structure, organs and tissues ubiquity, extremely wide variety of functions (proinflammatory cytokine, enzyme, hormone, ability to be induced by glucocorticoid hormones and affects as their immunosuppressive effects antagonist. MIF exists in preformed condition in lymphocytes, macrophages and endothelium cells. It secrets by these cells and operates as a mobilizing defense system factor in the first minutes of foreign invasion. MIF exhibits the properties of super-ligand binding with many biologically important molecules. This factor carries out the functions that are important for cell activation, proliferation and death, using a variety of intracellular signaling pathways. Some of MIF homologues exists in plants and bacteria earlier than innate and adaptive immune systems appears in evolution. In ontogenesis MIF appears at the stage of firsts cell divisions. MIF has a lot of functions, variety of ligand bindings, many effector pathways, it appears early in ontogeny and phylogeny. MIF takes part into protective reactions at any levels – from cell up to whole organism. All these MIF features taking together into account make it possible to possess it as a particular type of cytokine – eocytokine (from Greek word “eo” – early. It is assumed that MIF may function as some kind of cells and organisms "natural stability" key factor.

  8. Protective and pro-inflammatory roles of intestinal bacteria.

    Science.gov (United States)

    Reinoso Webb, Cynthia; Koboziev, Iurii; Furr, Kathryn L; Grisham, Matthew B

    2016-06-01

    The intestinal mucosal surface in all vertebrates is exposed to enormous numbers of microorganisms that include bacteria, archaea, fungi and viruses. Coexistence of the host with the gut microbiota represents an active and mutually beneficial relationship that helps to shape the mucosal and systemic immune systems of both mammals and teleosts (ray-finned fish). Due to the potential for enteric microorganisms to invade intestinal tissue and induce local and/or systemic inflammation, the mucosal immune system has developed a number of protective mechanisms that allow the host to mount an appropriate immune response to invading bacteria, while limiting bystander tissue injury associated with these immune responses. Failure to properly regulate mucosal immunity is thought to be responsible for the development of chronic intestinal inflammation. The objective of this review is to present our current understanding of the role that intestinal bacteria play in vertebrate health and disease. While our primary focus will be humans and mice, we also present the new and exciting comparative studies being performed in zebrafish to model host-microbe interactions. PMID:26947707

  9. Antimicrobial activity of amazonian medicinal plants

    OpenAIRE

    Oliveira, Amanda A; Segovia, Jorge FO; Sousa, Vespasiano YK; Mata, Elida CG; Gonçalves, Magda CA; Bezerra, Roberto M; Junior, Paulo OM; Kanzaki, Luís IB

    2013-01-01

    Objectives The aqueous extracts of currently utilized Amazonian medicinal plants were assayed in vitro searching for antimicrobial activity against human and animal pathogenic microorganisms. Methods Medium resuspended lyophilized aqueous extracts of different organs of Amazonian medicinal plants were assayed by in vitro screening for antimicrobial activity. ATCC and standardized microorganisms obtained from Oswaldo Cruz Foundation/Brazil were individually and homogeneously grown in agar plat...

  10. Antimicrobial Activity of Drosera rotundifolia L.

    OpenAIRE

    Miroslava Kačániová; Dominika Ďurechová; Nenad Vuković; Attila Kántor; Jana Petrová; Lukáš Hleba; Alexander Vatľák

    2014-01-01

    Droseracae spp. is widely used in folk medicine. In the present study, the antimicrobial activities of the four Drosera rotundifolia L. (D8.11, D15.12, 18.10, 8.11) samples were investigated. The antimicrobial activities were determined by using agar disc diffusion method against grampositive bacteria (Bacillus thurigiensis, Staphylococcus aureus, Listeria monocytogenes) and gramnegative bacteria (Yersinia enterocolitica, Salmonella enteritidis).  The results of the disk diffusion method show...

  11. The antimicrobial activity of Physalis peruviana L.

    OpenAIRE

    Göztok, Ferda; Zengin, Fikriye

    2013-01-01

    In this study, the antimicrobial activity of Physalis peruviana L. was investigated. The antimicrobial activity was evaluated according to the microdilution method by using Bacillus megaterium DMS 32, Pseudomonas aeruginosa DMS 50071, Escherichia coli ATCC 25922, Klebsiella pneumoniae FMC 5, Proteus vulgaris FMC 1, Enterobacter aeregenes CCM 2531, Candida albicans FMC 17, Candida globrata ATCC 66032, Candida tropicalis ATCC 13803, Trichophyton sp. and Epidermaphyton sp. In the end of experim...

  12. Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man

    DEFF Research Database (Denmark)

    Antonova, Maria; Wienecke, Troels; Olesen, Jes;

    2011-01-01

    During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E(2), prostaglandin I(2) (prostacyclin) and prostaglandin D(2) were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilata...... and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F(2α) (PGF(2α)) would cause headache in a human model of headache....

  13. Histamine mediates the pro-inflammatory effect of latex of Calotropis procera in rats

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    Yatin M. Shivkar

    2003-01-01

    Full Text Available Introduction: Calotropis procera is known to produce contact dermatitis and the latex of this plant produces intense inflammation when injected locally. However, the precise mode of its pro-inflammatory effect is not known. In present study we have pharmacologically characterized the inflammation induced by latex of C. procera in a rat paw edema model and determined the role of histamine in latex-induced inflammation.

  14. Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNγ in cerebrospinal fluid

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    Schaller Carlo

    2008-12-01

    Full Text Available Abstract Background In human neonatal high pressure hydrocephalus (HPHC, diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF concentrations of IL18, IFNγ and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively. Methods In neonatal HPHC (n = 30 and controls (n = 15, we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20, aqueduct stenosis (n = 4, and fetal intra-cerebral haemorrhage (n = 6. Neonatal control CSF was derived from otherwise healthy neonates (n = 15, who underwent lumbar puncture for exclusion of meningitis. Results In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values. Conclusion Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ in the CSF, whereas CSF apoptosis biomarkers (sFasL were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting could be helpful to preserve cerebral white matter.

  15. Entamoeba histolytica cysteine proteinase 5 binds integrin on colonic cells and stimulates NFkappaB-mediated pro-inflammatory responses.

    Science.gov (United States)

    Hou, Yongzhong; Mortimer, Leanne; Chadee, Kris

    2010-11-12

    Integrins are important mammalian receptors involved in normal cellular functions and the pathogenesis of inflammation and disease. Entamoeba histolytica is a protozoan parasite that colonizes the gut, and in 10% of infected individuals, causes amebic colitis and liver abscess resulting in 10(5) deaths/year. E. histolytica-induced host inflammatory responses are critical in the pathogenesis of the disease, yet the host and parasite factors involved in disease are poorly defined. Here we show that pro-mature cysteine proteinase 5 (PCP5), a major virulent factor that is abundantly secreted and/or present on the surface of ameba, binds via its RGD motif to α(V)β(3) integrin on Caco-2 colonic cells and stimulates NFκB-mediated pro-inflammatory responses. PCP5 RGD binding to α(V)β(3) integrin triggered integrin-linked kinase(ILK)-mediated phosphorylation of Akt-473 that bound and induced the ubiquitination of NF-κB essential modulator (NEMO). As NEMO is required for activation of the IKKα-IKKβ complex and NFκB signaling, these events markedly up-regulated pro-inflammatory mediator expressions in vitro in Caco-2 cells and in vivo in colonic loop studies in wild-type and Muc2(-/-) mice lacking an intact protective mucus barrier. These results have revealed that EhPCP5 RGD motif is a ligand for α(V)β(3) integrin-mediated adhesion on colonic cells and represents a novel mechanism that E. histolytica trophozoites use to trigger an inflammatory response in the pathogenesis of intestinal amebiasis.

  16. The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases

    Science.gov (United States)

    van den Bosch, Thea; Boichenko, Alexander; Leus, Niek G. J.; Eleni Ourailidou, Maria; Wapenaar, Hannah; Rotili, Dante; Mai, Antonello; Imhof, Axel; Bischoff, Rainer; Haisma, Hidde J.; Dekker, Frank J.

    2016-01-01

    Lysine acetylations are reversible posttranslational modifications of histone and non-histone proteins that play important regulatory roles in signal transduction cascades and gene expression. Lysine acetylations are regulated by histone acetyltransferases as writers and histone deacetylases as erasers. Because of their role in signal transduction cascades, these enzymes are important players in inflammation. Therefore, applications of histone acetyltransferase inhibitors to reduce inflammatory responses are interesting. Among the few histone acetyltransferase inhibitors described, C646 is one of the most potent (Ki of 0.4 μM for histone acetyltransferase p300). C646 was described to regulate the NF-κB pathway; an important pathway in inflammatory responses, which is regulated by acetylation. Interestingly, this pathway has been implicated in asthma and COPD. Therefore we hypothesized that via regulation of the NF-κB signaling pathway, C646 can inhibit pro-inflammatory gene expression, and have potential for the treatment of inflammatory lung diseases. In line with this, here we demonstrate that C646 reduces pro-inflammatory gene expression in RAW264.7 murine macrophages and murine precision-cut lung slices. To unravel its effects on cellular substrates we applied mass spectrometry and found, counterintuitively, a slight increase in acetylation of histone H3. Based on this finding, and structural features of C646, we presumed inhibitory activity of C646 on histone deacetylases, and indeed found inhibition of histone deacetylases from 7 μM and higher concentrations. This indicates that C646 has potential for further development towards applications in the treatment of inflammation, however, its newly discovered lack of selectivity at higher concentrations needs to be taken into account. PMID:26718586

  17. Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages

    International Nuclear Information System (INIS)

    Background and purpose: Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE−/− mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo. Material and methods: ApoE−/− mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro. Results: Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages. Conclusions: Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque

  18. Extracellular histone H1 is neurotoxic and drives a pro-inflammatory response in microglia [v1; ref status: indexed, http://f1000r.es/18z

    Directory of Open Access Journals (Sweden)

    Jonathan D Gilthorpe

    2013-07-01

    Full Text Available In neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B H3 and H4 were not neurotoxic. Innate immunity in the central nervous system is mediated through microglial cells and we show here for the first time that histone H1 promotes their survival, up-regulates MHC class II antigen expression and is a powerful microglial chemoattractant. We propose that when the central nervous system is degenerating, histone H1 drives a positive feedback loop that drives further degeneration and activation of immune defences which can themselves be damaging. We suggest that histone H1 acts as an antimicrobial peptide and kills neurons through mitochondrial damage and apoptosis.

  19. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms

    OpenAIRE

    Aschbacher, K; Epel, E; Wolkowitz, O M; Prather, A A; Puterman, E; Dhabhar, F.S.

    2011-01-01

    Cognitive and affective responses to acute stress influence pro-inflammatory cytokine reactivity, and peripheral cytokines (particularly lnterleukin-1 beta (IL-1β)), can act on the brain to promote depressive symptoms. It is unknown whether acute stress-induced changes in positive affect and cognitions (POS) and pro-inflammatory reactivity predict future depressive symptoms. We examined acute stress responses among women, to determine prospective predictors of depressive symptoms. Hypotheses:...

  20. A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Brix, Thomas H; Leslie, R Graham Q;

    2009-01-01

    individuals with no familiar disposition to AITD, and mixed each serum with normal mononuclear cells (MNCs). Following challenge with TPO, the MNCs' production of the pro-inflammatory cytokines TNF-alpha, IL-6 and IFN-gamma, and the anti-inflammatory cytokine IL-10, correlated with the TPOAb content...... that TPO-induced release of pro-inflammatory cytokines from phagocytic cells and T-cell responses to TPO are promoted by TPOAbs....

  1. 促/抑炎因子平衡在反复胚胎种植失败中的作用%Effect of pro-inflammatory and anti-inflammatory cytokine balance on recurrent implantation failure

    Institute of Scientific and Technical Information of China (English)

    梁佩燕; 李观贵; 连若纯; 陈晓燕; 曾勇

    2013-01-01

    The balance of pro-inflammatory and anti-inflammatory cytokine plays a significant role on the process of embryo implantation and pregnancy. However, the imbalance of these cytokines is probably one of the most important causes of recurrent implantation failure. On one hand,the higher pro-inflammatory cytokine or insufficient anti-inflammatory cytokine may activate the immune cells(NK cell, macrophage and T cell) at the fetal-maternal interface, which probably attacks the trophoblast cells and promotes the formation of thrombus in the villous vessels,thus leads to the immunological rejection to the fetus, implantation failure, early pregnant loss and contributes to the pregnancy complication such as intrauterine growth retardation, preeclampsia and preterm labor. On the other hand, lower pro-inflammatory cytokine or higher anti-inflammatory cytokine may influence the embryo adhesion to endometrium and angiogenesis, which results in implantation failure. In conclusion, the bias of the pro-inflammatory or anti-inflammatory cytokine is probably detrimental to uterine receptivity and implantation.

  2. ANTIMICROBIAL ACTIVITY OF FICUS GLOMERATA LINN. BARK

    Directory of Open Access Journals (Sweden)

    Jagtap Supriya G.

    2012-05-01

    Full Text Available Ficus glomerata Linn. (Moraceae, commonly known as Ficus racemosa. A large deciduous tree distributed all over India and Ceylon, found throughout the year, grows in evergreen forest, moist localities, along the sides of ravines and banks of streams. Gular (Ficus glomerata Linn. is well known, commonly used plant in various disorders. It has been traditionally claimed to be useful in asthmatic condition, as an antitussive and anti-inflammatory. Successive soxhlet extractions of dried powdered bark were carried out using petroleum ether and methanol as a solvent. The antimicrobial activity of the extracts were tested in vitro against two different bacterial species Bacillus substilis and Escherichia coli by cup plate diffusion method were used in this investigation. The results of antimicrobial activity revealed that methanolic extract showed good activity as compared to petroleum ether extract. Methanolic extract is more potent towards gram - positive bacteria. The antimicrobial activities of the extracts were compared with standard antibiotics.

  3. The Antimicrobial Activity of Porphyrin Attached Polymers

    Science.gov (United States)

    Thompson, Lesley

    2008-03-01

    We are interested in testing the antimicrobial activity of a porphyrin that is attached to a polymer. The porphyrin (5-(4-carboxyphenyl)-10,15,20-tris-(4-pryridyl)) was synthesized from methyl 4-formyl benzoate, 4-pyridinecarboxaldehyde, and pyrrole and attached to a copolymer of polystyrene/poly(vinyl benzyl chloride), which was synthesized by free radical polymerization. The antimicrobial activity of the polymer-attached porphyrin was then determined for gram-negative E. Coli grown to 0.80 OD. In this procedure, glass slides were coated with polymer-attached porphyrin via dip-coating, and the E. Coli bacteria were plated in Luria Broth media. The plates were subsequently exposed to light overnight before they were incubated as porphyrins act as photo-sensitizers when irradiated with light. The polymer-attached porphyrin did exhibit antimicrobial activity and parameters that affect its efficiency will be discussed.

  4. Retracted: Effects of pro-inflammatory cytokines on mineralization potential of rat dental pulp stem cells.

    Science.gov (United States)

    2011-10-01

    The following article from the Journal of Tissue Engineering and Regenerative Medicine, 'Effects of Pro-inflammatory Cytokines on Mineralization Potential of Rat Dental Pulp Stem Cells' by Yang X, Walboomers XF, Bian Z, Jansen JA, Fan M, published online on 11 July 2011 in Wiley Online Library (onlinelibrary.wiley.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, and John Wiley & Sons, Ltd. The retraction has been agreed due to two authors (Walboomers XF, and Jansen JA) not having been involved in the research described, nor made aware of their names being listed on the manuscript, nor told of its submission to the journal.

  5. Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway

    DEFF Research Database (Denmark)

    Maddahi, Aida; Edvinsson, Lars

    2010-01-01

    levels of pro-inflammatory mediators in the infarct region. In this study, we hypothesised that inhibition of the cerebrovascular inflammatory reaction with a specific MEK1/2 inhibitor (U0126) to block transcription or a combined receptor blockade would reduce infarct size and improve neurological score...... and endothelin ETA receptors decreased the volume of brain damaged (12.3 +/- 3; P cytokines CONCLUSION: The present study shows elevated microvascular expression of TNF-alpha, IL-1ss, IL-6 and iNOS following focal ischemia, and shows...

  6. Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow concentrations of silver, titanium dioxide, and zinc oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Giovanni, Marcella [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585 (Singapore); Yue, Junqi; Zhang, Lifeng [PUB, 40 Scotts Road, Singapore 228231 (Singapore); Xie, Jianping [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585 (Singapore); Ong, Choon Nam [Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, Singapore 117549 (Singapore); NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411 (Singapore); Leong, David Tai, E-mail: cheltwd@nus.edu.sg [Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585 (Singapore)

    2015-10-30

    Highlights: • Ultralow levels of common nanoparticles exist in environment and consumer products. • Common nanoparticles at ultralow levels induce mild pro-inflammation by macrophages. • The nanoparticles are cytotoxic only at high doses. - Abstract: To cellular systems, nanoparticles are considered as foreign particles. Upon particles and cells contact, innate immune system responds by activating the inflammatory pathway. However, excessive inflammation had been linked to various diseases ranging from allergic responses to cancer. Common nanoparticles, namely silver, titanium dioxide, and zinc oxide exist in the environment as well as in consumer products at ultralow level of 10{sup −6}–10{sup −3} μg mL{sup −1}. However, so far the risks of such low NPs concentrations remain unexplored. Therefore, we attempted to screen the pro-inflammatory responses after ultralow concentration treatments of the three nanoparticles on RAW264.7 macrophages, which are a part of the immune system, at both cellular and gene levels. Even though cytotoxicity was only observed at nanoparticles concentrations as high as 10 μg mL{sup −1}, through the level of NF-κB and upregulation of pro-inflammatory genes, we observed activation of the induction of genes encoding pro-inflammatory cytokines starting already at 10{sup −7} μg mL{sup −1}. This calls for more thorough characterization of nanoparticles in the environment as well as in consumer products to ascertain the health and safety of the consumers and living systems in general.

  7. Antimicrobial Activity of Carbon-Based Nanoparticles

    Directory of Open Access Journals (Sweden)

    Solmaz Maleki Dizaj

    2015-03-01

    Full Text Available Due to the vast and inappropriate use of the antibiotics, microorganisms have begun to develop resistance to the commonly used antimicrobial agents. So therefore, development of the new and effective antimicrobial agents seems to be necessary. According to some recent reports, carbon-based nanomaterials such as fullerenes, carbon nanotubes (CNTs (especially single-walled carbon nanotubes (SWCNTs and graphene oxide (GO nanoparticles show potent antimicrobial properties. In present review, we have briefly summarized the antimicrobial activity of carbon-based nanoparticles together with their mechanism of action. Reviewed literature show that the size of carbon nanoparticles plays an important role in the inactivation of the microorganisms. As major mechanism, direct contact of microorganisms with carbon nanostructures seriously affects their cellular membrane integrity, metabolic processes and morphology. The antimicrobial activity of carbon-based nanostructures may interestingly be investigated in the near future owing to their high surface/volume ratio, large inner volume and other unique chemical and physical properties. In addition, application of functionalized carbon nanomaterials as carriers for the ordinary antibiotics possibly will decrease the associated resistance, enhance their bioavailability and provide their targeted delivery.

  8. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells

    Directory of Open Access Journals (Sweden)

    Murphy Fiona A

    2012-04-01

    Full Text Available Abstract Carbon nanotubes (CNT are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.

  9. Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.

    Science.gov (United States)

    Han, Xiao-qun; Gong, Zuo-jiong; Xu, San-qing; Li, Xun; Wang, Li-kun; Wu, Shi-min; Wu, Jian-hong; Yang, Hua-fen

    2014-02-01

    This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It

  10. Antimicrobial activity of mangrove plant (Lumnitzera littorea)

    Institute of Scientific and Technical Information of China (English)

    Shahbudin Saad; Muhammad Taher; Deny Susanti; Haitham Qaralleh; Nurul Afifah Binti Abdul Rahim

    2011-01-01

    Objective:To investigate the antimicrobial activities ofn-hexane, ethyl acetate and methanol extracts of the leaves ofLumnitzera littorea (L. littorea) against six human pathogenic microbes. Methods: The antimicrobial activity was evaluated using disc diffusion and microdilution methods.Results:The antimicrobial activities of the crude extracts were increased with increasing the concentration. It is clear thatn-hexane extract was the most effective extract. Additionally, Gram positiveBacillus cereus (B. cereus) appear to be the most sensitive strain whilePseudomonas aeruginosa (P. aeruginosa) and the yeast strains (Candida albicans (C. albicans) andCryptococcus neoformans (C. neoformans)) appear to be resistance to the tested concentrations since no inhibition zone was observed. The inhibition of microbial growth at concentration as low as0.04 mg/mL indicated the potent antimicrobial activity ofL. littorea extracts.Conclusions:The obtained results are considered sufficient for further study to isolate the compounds responsible for the activity and suggesting the possibility of finding potent antibacterial agents fromL. littorea extracts.

  11. Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis.

    LENUS (Irish Health Repository)

    McNally, P

    2011-07-22

    BACKGROUND: 1,25-Dihydroxycholecalciferol (1,25(OH)(2)D(3)) has been shown to mitigate epithelial inflammatory responses after antigen exposure. Patients with cystic fibrosis (CF) are at particular risk for vitamin D deficiency. This may contribute to the exaggerated inflammatory response to pulmonary infection in CF. METHODS: CF respiratory epithelial cell lines were exposed to Pseudomonas aeruginosa lipopolysaccharide (LPS) and Pseudomonas conditioned medium (PCM) in the presence or absence of 1,25(OH)(2)D(3) or a range of vitamin D receptor (VDR) agonists. Levels of IL-6 and IL-8 were measured in cell supernatants, and cellular total and phosphorylated IκBα were determined. Levels of human cathelicidin antimicrobial peptide (hCAP18) mRNA and protein were measured in cells after treatment with 1,25(OH)(2)D(3). RESULTS: Pretreatment with 1,25(OH)(2)D(3) was associated with significant reductions in IL-6 and IL-8 protein secretion after antigen exposure, a finding reproduced with a range of low calcaemic VDR agonists. 1,25(OH)(2)D(3) treatment led to a decrease in IκBα phosphorylation and increased total cellular IκBα. Treatment with 1,25(OH)(2)D(3) was associated with an increase in hCAP18\\/LL-37 mRNA and protein levels. CONCLUSIONS: Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.

  12. The antimicrobial efficiency of silver activated sorbents

    Science.gov (United States)

    Đolić, Maja B.; Rajaković-Ognjanović, Vladana N.; Štrbac, Svetlana B.; Rakočević, Zlatko Lj.; Veljović, Đorđe N.; Dimitrijević, Suzana I.; Rajaković, Ljubinka V.

    2015-12-01

    This study is focused on the surface modifications of the materials that are used for antimicrobial water treatment. Sorbents of different origin were activated by Ag+-ions. The selection of the most appropriate materials and the most effective activation agents was done according to the results of the sorption and desorption kinetic studies. Sorption capacities of selected sorbents: granulated activated carbon (GAC), zeolite (Z), and titanium dioxide (T), activated by Ag+-ions were following: 42.06, 13.51 and 17.53 mg/g, respectively. The antimicrobial activity of Ag/Z, Ag/GAC and Ag/T sorbents were tested against Gram-negative bacteria E. coli, Gram-positive bacteria S. aureus and yeast C. albicans. After 15 min of exposure period, the highest cell removal was obtained using Ag/Z against S. aureus and E. coli, 98.8 and 93.5%, respectively. Yeast cell inactivation was unsatisfactory for all three activated sorbents. The antimicrobial pathway of the activated sorbents has been examined by two separate tests - Ag+-ions desorbed from the activated surface to the aqueous phase and microbial cell removal caused by the Ag+-ions from the solid phase (activated surface sites). The results indicated that disinfection process significantly depended on the microbial-activated sites interactions on the modified surface. The chemical state of the activating agent had crucial impact to the inhibition rate. The characterization of the native and modified sorbents was performed by X-ray diffraction technique, X-ray photoelectron spectroscopy and scanning electron microscope. The concentration of adsorbed and released ions was determined by inductively coupled plasma optical emission spectroscopy and mass spectrometry. The antimicrobial efficiency of activated sorbents was related not only to the concentration of the activating agent, but moreover on the surface characteristics of the material, which affects the distribution and the accessibility of the activating agent.

  13. Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: implications for laminitis.

    Science.gov (United States)

    de Laat, M A; Clement, C K; McGowan, C M; Sillence, M N; Pollitt, C C; Lacombe, V A

    2014-01-15

    Equine laminitis, a disease of the lamellar structure of the horse's hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Toll-like receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-α and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-α, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However

  14. Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering

    Directory of Open Access Journals (Sweden)

    Sudhir H. Ranganath

    2016-06-01

    Full Text Available Mesenchymal stromal cells (MSCs are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.

  15. 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways.

    Science.gov (United States)

    DelNero, Peter; Lane, Maureen; Verbridge, Scott S; Kwee, Brian; Kermani, Pouneh; Hempstead, Barbara; Stroock, Abraham; Fischbach, Claudia

    2015-07-01

    Oxygen status and tissue dimensionality are critical determinants of tumor angiogenesis, a hallmark of cancer and an enduring target for therapeutic intervention. However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. In particular, interleukin-8 (IL-8) emerged as a major player in the microenvironmental regulation of the hypoxia program. Notably, this interaction between dimensionality and oxygen status via IL-8 increased angiogenic sprouting in a 3D endothelial invasion assay. Taken together, our data suggest that pro-inflammatory pathways are critical regulators of tumor hypoxia response within 3D environments that ultimately impact tumor angiogenesis, potentially providing important therapeutic targets. Furthermore, these results highlight the importance of pathologically relevant tissue culture models to study the complex physical and chemical processes by which the cancer microenvironment mediates new vessel formation.

  16. Absent in Melanoma 2 (AIM2) limits pro-inflammatory cytokine transcription in cardiomyocytes by inhibiting STAT1 phosphorylation.

    Science.gov (United States)

    Furrer, Antonia; Hottiger, Michael O; Valaperti, Alan

    2016-06-01

    Interferon (IFN)-γ is highly upregulated during heart inflammation and enhances the production of pro-inflammatory cytokines. Absent in Melanoma 2 (AIM2) is an IFN-inducible protein implicated as a component of the inflammasome. Here we seek to determine the role of AIM2 during inflammation in cardiac cells. We found that the presence of AIM2, but not of the other inflammasome components Nod-like receptor (NLR) NLRP3 or NLRC4, specifically limited the transcription of the pro-inflammatory cytokines interleukin (IL)-6, IP-10, and tumor necrosis factor (TNF)-α in HL-1 mouse cardiomyocytes stimulated with IFN-γ and lipopolysaccharides (LPS). Similarly, AIM2 reduced pro-inflammatory cytokine transcription in primary mouse neonatal cardiomyocytes (MNC), but not in primary mouse neonatal cardiac fibroblasts (MNF). Interestingly, AIM2-dependent reduction of pro-inflammatory cytokines in cardiomyocytes was independent of Caspase-1. Mechanistically, AIM2 reduced pro-inflammatory cytokine transcription in cardiomyocytes by interacting with and inhibiting the phosphorylation of STAT1. In AIM2-depleted cardiomyocytes, increased STAT1 phosphorylation enhanced the NF-κB pathway by promoting NF-κB p65 phosphorylation and acetylation. These results show for the first time that AIM2 plays an important anti-inflammatory, yet inflammasome-independent function in cardiomyocytes. Our findings will help to further understand how the various heart cell types differently react to inflammatory stimuli. PMID:27148820

  17. A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells

    International Nuclear Information System (INIS)

    Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors. Incubation of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NFκB and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCP1, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo

  18. Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

    Directory of Open Access Journals (Sweden)

    Ruthazer Edward S

    2010-01-01

    Full Text Available Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the

  19. Co-stimulation-induced release of pro-inflammatory cytokine interleukin-8 by allergen-specific T cells.

    Science.gov (United States)

    Spinozzi, F; Agea, E; Piattoni, S; Bistoni, O; Grignani, F; Bertotto, A

    1996-07-01

    Chemokines, which include interleukin (IL)-8, are a family of pro-inflammatory molecules with potent chemoattractant activity on neutrophils, as well as other cell types. IL-8 can be recovered from many inflammatory sites. To test the hypothesis that Th2-type allergen-specific T cells, known to be the main cell type governing the allergic inflammation, are a source of IL-8 and to investigate whether IL-8 release is influenced by the nature of the in vitro mitogenic or co-mitogenic stimulation, cypress-specific T-cell clones (TCC) were generated from five allergic subjects during in vitro seasonal exposure to the allergen. Purified cypress extract was produced directly from freshly collected pollen and used for in vitro stimulation of PBMC bulk cultures. After 5 days priming and a further 7 day period of IL-2-driven cell expansion, monoclonal antibodies to CD3, CD2 and CD28 were adopted for in vitro restimulation of allergen-specific cell lines or, subsequently, secondary established TCC. The induction of apoptosis was detected by propidium iodide (PI) cytofluorimetric assay. Basal and co-stimulation-induced IL-8 production was measured by an ELISA method. Both cypress-specific T-cell lines and TCC secreted appreciable amounts of IL-8. By cross-linking T-cell lines or Th2 CD4+ TCC with CD3, CD2 or CD28 MoAbs, the authors observed a great stimulation-induced IL-8 secretion, preferentially after CD2 or combined CD2/CD28 stimulation. In addition, CD4+ clones released large amounts of IL-8 into culture supernatants after CD2 stimulation while undergoing programmed cell death (30-40% hypodiploid DNA profile of PI-stained cells). In contrast, CD3 crosslinking was unable to determine the release of IL-8 or the induction of apoptosis. Taken together, these results suggest that incomplete TcR engagement by allergen may lead to the secretion of pro-inflammatory cytokines with a contemporary induction of apoptosis in a significant number of target cells. This phenomenon may

  20. Antimicrobial activity of Aspilia latissima (Asteraceae

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    Jeana M.E. Souza

    2015-12-01

    Full Text Available Abstract We evaluated the antimicrobial activity of Aspilia latissima - an abundant plant from the Brazilian Pantanal region - against Candida albicans, Candida parapsilosis, Candida krusei, Candida tropicalis, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli and Staphylococcus aureus. The crude extracts and fractions showed activity in all tested microorganisms. The chloroform fraction of the leaves and roots showed the most antimicrobial activity against S. aureus, with an MIC of 500 μg/mL. This fraction was submitted to bioautographic assays to characterize the activity of the compounds. Two bands from the leaves (L-A and L-B and three bands from the roots (R-C, R-D and R-E were bioactive. Within the root-derived bands, the terpene derivatives stigmasterol, kaurenoic acid and kaura-9(11, 16-dien-18-oic acid were identified. Antibiotic activity of A. latissima is reported for the first time.

  1. Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

    Science.gov (United States)

    McGuire, Victoria A.; Ruiz-Zorrilla Diez, Tamara; Emmerich, Christoph H.; Strickson, Sam; Ritorto, Maria Stella; Sutavani, Ruhcha V.; Weiβ, Anne; Houslay, Kirsty F.; Knebel, Axel; Meakin, Paul J.; Phair, Iain R.; Ashford, Michael L. J.; Trost, Matthias; Arthur, J. Simon C.

    2016-01-01

    Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity. PMID:27498693

  2. Transcriptional Activation of Inflammatory Genes: Mechanistic Insight into Selectivity and Diversity.

    Science.gov (United States)

    Ahmed, Afsar U; Williams, Bryan R G; Hannigan, Gregory E

    2015-11-11

    Acute inflammation, an integral part of host defence and immunity, is a highly conserved cellular response to pathogens and other harmful stimuli. An inflammatory stimulation triggers transcriptional activation of selective pro-inflammatory genes that carry out specific functions such as anti-microbial activity or tissue healing. Based on the nature of inflammatory stimuli, an extensive exploitation of selective transcriptional activations of pro-inflammatory genes is performed by the host to ensure a defined inflammatory response. Inflammatory signal transductions are initiated by the recognition of inflammatory stimuli by transmembrane receptors, followed by the transmission of the signals to the nucleus for differential gene activations. The differential transcriptional activation of pro-inflammatory genes is precisely controlled by the selective binding of transcription factors to the promoters of these genes. Among a number of transcription factors identified to date, NF-κB still remains the most prominent and studied factor for its diverse range of selective transcriptional activities. Differential transcriptional activities of NF-κB are dictated by post-translational modifications, specificities in dimer formation, and variability in activation kinetics. Apart from the differential functions of transcription factors, the transcriptional activation of selective pro-inflammatory genes is also governed by chromatin structures, epigenetic markers, and other regulators as the field is continuously expanding.

  3. ANTIMICROBIAL ACTIVITY OF TINOSPORA CRISPA ROOT EXTRACTS

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    Asif Iqbal Chittur Mohammed

    2012-06-01

    Full Text Available The aim of this study was to determine the in vitro antimicrobial activity of ethanol, distilled water, methanol and chloroform crude extracts of the roots of Tinospora crispa. Antimicrobial activity was examined by disc diffusion method against gram positive bacterial strains of Streptococcus pneumonia, gram negative bacterial strains of Escherichia coli and fungal strains of Candida albicans. The maximum zone of inhibition was obtained with ethanol extract against Escherichia coli and Streptococcus pneumonia followed by chloroform extract against the same organisms. Whilst distilled water extract showed a minimal zone of inhibition, methanol extract showed a moderate zone of inhibition against the bacterial strains used. The values were compared with a standard antibiotic. The ethanol extract also showed the maximum zone of inhibition against the growth of Candida albicans, whereas the lowest activity was shown with distilled water crude extract. Methanol and chloroform crude extracts showed considerably moderate activities against the fungal strain, as compared to the standard antibiotic used.

  4. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    Science.gov (United States)

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP.

  5. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    Science.gov (United States)

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP. PMID:27318790

  6. IN-VITRO ANTIMICROBIAL ACTIVITY OF BRONCHOSOL.

    Science.gov (United States)

    Witkowska-Banaszczak, Ewa; Michalak, Anna; Kędzia, Anna

    2015-01-01

    Bronchosol is a traditional medicinal product in the form of syrup used in cough and impeded expectoration. The active ingredients that it contains include extracts from the herb of thyme, the root of primrose and thymol. It is recommended in disorders of the respiratory tract when expectoration is impeded and secretion of liquid mucus in bronchi is insufficient. Antimicrobial activity of the components of Bronchosol, especially thyme and thymol, has frequently been reported in the literature. To date, there have not been any studies to confirm such activity of Bronchosol, though. The results of our research are the first one to point to the great activity of Bronchosol against microorganisms causing infections of the respiratory tract. It has been demonstrated that this product displayed antimicrobial activity against reference strains as well as strains of anaerobic and aerobic bacteria and fungi isolated from patients. The confirmation of the antimicrobial activity of Bronchosol provides an explanation of its effectiveness in the therapy of the respiratory tract infections. PMID:26642688

  7. ANTIMICROBIAL ACTIVITY OF EXTRACTS FROM ECUADORIAN LICHENS.

    Science.gov (United States)

    Matvieieva, N A; Pasichnyk, L A; Zhytkevych, N V; Jacinto, Pabón Garcés Galo; Pidgorskyi, V S

    2015-01-01

    Antimicrobial activity of the ethanolic, isopropanolic, acetone, DMSO and aqueous extracts of the two lichen species from Ecuadorian highland, Usnea sp. and Stereocaulon sp. were explored in vitro against bacteria Bacillus subtilis, Escherichia coli and Staphylococcus aureus by the disc-diffusion method. Also the minimal inhibitory concentration (MIC) was determined. The strongest antimicrobial activity was found in DMSO extract of Usnea sp. compared to antibacterial activity of ciprfloxacin and cefazolin antibiotics. The inhibition zone was 28 mm, 30 mm, 31mm (DMSO extract, ciprfloxacin and cefazolin respectively) in case of B. subtilis usage as the test bacteria. MIC value for Usnea sp. and Stereocaulon sp. DMSO extracts was 0.4 mg/ml. E. coli was resistant to all kinds of extracts. The S. aureus sensitivity to lichen DMSO extracts was comparable to sensitivity of these microorganisms to tetracycline and vancomycin. Thereby, most kinds of extracts (ethanol, isopropanol, hexane, DMSO and acetone solvents) from Ecuadorian lichens Usnea sp. and Stereocaulon sp. with the exception of aqueous Stereocaulon sp. extracts possessed antibacterial activity against B. subtilis. DMSO lichen extracts had also antimicrobial activity against S. aureus. At the same time the extracts studied didn't demonstrate antibacterial activity against the representatives of the most common and harmful phytopathogenic bacteria tested. Further investigations of Ecuadorian lichens especially study of plants collected from extremal highland biotops can be very important in study of possibility of treatment of numerous diseases caused by pathogenic microorganisms. PMID:26214895

  8. Magnesium Based Materials and their Antimicrobial Activity

    Science.gov (United States)

    Robinson, Duane Allan

    The overall goals of this body of work were to characterize the antimicrobial properties of magnesium (Mg) metal and nano-magnesium oxide (nMgO) in vitro, to evaluate the in vitro cytotoxicity of Mg metal, and to incorporate MgO nanoparticles into a polymeric implant coating and evaluate its in vitro antimicrobial properties. In the course of this work it was found that Mg metal, Mg-mesh, and nMgO have in vitro antimicrobial properties that are similar to a bactericidal antibiotic. For Mg metal, the mechanism of this activity appears to be related to an increase in pH (i.e. a more alkaline environment) and not an increase in Mg2+. Given that Mg-mesh is a Mg metal powder, the assumption is that it has the same mechanism of activity as Mg metal. The mechanism of activity for nMgO remains to be elucidated and may be related to a combination of interaction of the nanoparticles with the bacteria and the alkaline pH. It was further demonstrated that supernatants from suspensions of Mg-mesh and nMgO had the same antimicrobial effect as was noted when the particles were used. The supernatant from Mg-mesh and nMgO was also noted to prevent biofilm formation for two Staphylococcus strains. Finally, poly-epsilon-caprolactone (PCL) composites of Mg-mesh (PCL+Mg-mesh) and nMgO (PCL+nMgO) were produced. Coatings applied to screws inhibited growth of Escherichia coli and Pseudomonas aeruginosa and in thin disc format inhibited the growth of Staphylococcus aureus in addition to the E. coli and P. aeruginosa. Pure Mg metal was noted to have some cytotoxic effect on murine fibroblast and osteoblast cell lines, although this effect needs to be characterized further. To address the need for an in vivo model for evaluating implant associated infections, a new closed fracture osteomyelitis model in the femur of the rat was developed. Magnesium, a readily available and inexpensive metal was shown to have antimicrobial properties that appear to be related to its corrosion products and

  9. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks

    Science.gov (United States)

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells. PMID:27594840

  10. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.

    Science.gov (United States)

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

  11. Modeling the pro-inflammatory tumor microenvironment in acute lymphoblastic leukemia predicts a breakdown of hematopoietic-mesenchymal communication networks

    Directory of Open Access Journals (Sweden)

    Jennifer Enciso

    2016-08-01

    Full Text Available Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs and mesenchymal stromal cells (MSCs within the bone marrow. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

  12. Antioxidant and antimicrobial activities of Shorea kunstleri

    Institute of Scientific and Technical Information of China (English)

    Siti Suria Daud; Muhammad Taher; Deny Susanti

    2014-01-01

    Objective:To evaluate antioxidant and antimicrobial activities of stembark of Shorea kunstleri (S. kunstleri) together with analysis of phytochemical and total phenolic contents. Methods:Extraction was conducted with different solvent polarity of n-hexane, dichloromethane (DCM) and methanol by using Soxhlet extraction. Total phenolic content was determined using Folin-Ciocalteu method. Free radical scavenging activity and inhibition of lipid peroxidation were evaluated with DPPH radical scavenging and ferric thiocyanate assays, respectively. Antimicrobial activities were performed using disc diffusion method, minimum inhibition concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration. Results:S. kunstleri stembark extracts revealed presence of steroids, terpenoids, saponins, flavonoids, and phenolic compounds. Methanol extract exhibited the highest total phenolic content and free radical scavenging activity resulting in phenolic content of (8.340±0.003) g GAE/100 g of extract and (95.90±1.07)% DPPH inhibition (IC50 value of 18.6 µg/mL), respectively. Ferric thiocyanate assay of n-hexane, DCM, and methanol extracts indicated lipid peroxidation inhibitory activity of (74.20±0.35)%, (74.00±0.10)%, and (72.80±0.27)%, respectively. In antimicrobial and antifungal tests, methanol extract showed inhibition against Staphylococcus aureus (S. aureus), Candida albicans, and Candida tropicalis with inhibition zones of 10-12, 18-22, and 18-19 mm, respectively. The MIC test of methanol extract showed highest inhibition against Candida albicans and S. aureus (0.04 and 0.08 mg/mL, respectively) while DCM extract exhibited the highest activity towards Candida tropicalis (MIC value of 0.63 mg/mL). Taken together, MBC test of methanol extract strongly demonstrated bactericidal effect against S. aureus with MBC value of 0.08 mg/mL. Conclusions:The study demonstrated that stembark extracts of S. kunstleri possessed antioxidant and

  13. Antimicrobial activity of Michelia champaca.

    Science.gov (United States)

    Khan, M R; Kihara, M; Omoloso, A D

    2002-12-01

    The methanol extracts of leaves, seeds, stem and root barks, stem and root heart-woods of Michelia champaca and the obtained fractions (petrol, dichloromethane, ethyl acetate, butanol) exhibited a broad spectrum of antibacterial activity. Fractionation drastically enhanced the level of activity particularly in all fractions of the stem bark and dichloromethane fraction of the root bark. Some fractions of the leaves, stem and root barks demonstrated antifungal activity against some of the tested moulds. Liriodenine was the active constituent of the root bark, with a broader and, in some cases, better level of activity as compared to the standard. PMID:12490248

  14. Pulsed ultrasound associated with gold nanoparticle gel reduces oxidative stress parameters and expression of pro-inflammatory molecules in an animal model of muscle injury

    Directory of Open Access Journals (Sweden)

    Victor Eduardo G

    2012-03-01

    Full Text Available Abstract Background Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound with gold nanoparticles (GNP on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury. Materials and methods Animals were divided in nine groups: sham (uninjured muscle; muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α were measured as inflammatory parameters. Results Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p Conclusions Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.

  15. In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: impact of physico-chemical features on pro-inflammatory and pro-oxidative effects.

    Science.gov (United States)

    Boudard, Delphine; Forest, Valérie; Pourchez, Jérémie; Boumahdi, Najih; Tomatis, Maura; Fubini, Bice; Guilhot, Bernard; Cottier, Michèle; Grosseau, Philippe

    2014-08-01

    Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H₂O₂ production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650-1400 °C) in order to alter the oxidation state of the particle surface. At 1400 °C a decrease in TNFα production and an increase in HO·, COO(·-) radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity. PMID:24603312

  16. MK615 attenuates Porphyromonas gingivalis lipopolysaccharide-induced pro-inflammatory cytokine release via MAPK inactivation in murine macrophage-like RAW264.7 cells.

    Science.gov (United States)

    Morimoto, Yoko; Kikuchi, Kiyoshi; Ito, Takashi; Tokuda, Masayuki; Matsuyama, Takashi; Noma, Satoshi; Hashiguchi, Teruto; Torii, Mitsuo; Maruyama, Ikuro; Kawahara, Ko-Ichi

    2009-11-01

    The Japanese apricot, known as Ume in Japanese, has been a traditional Japanese medicine for centuries, and is a familiar and commonly consumed food. The health benefits of Ume are now being widely recognized and have been strengthened by recent studies showing that MK615, an extract of compounds from Ume, has strong anticancer and anti-inflammatory effects. However, the potential role of MK615 in the periodontal field remains unknown. Here, we found that MK615 significantly reduced the production of pro-inflammatory mediators (tumor necrosis factor-alpha and interleukin-6) induced by Porphyromonas gingivalis lipopolysaccharide (LPS), a major etiological agent in localized chronic periodontitis, in murine macrophage-like RAW264.7 cells. MK615 markedly inhibited the phosphorylation of ERK1/2, p38MAPK, and JNK, which is associated with pro-inflammatory mediator release pathways. Moreover, MK615 completely blocked LPS-triggered NF-kappaB activation. The present results suggest that MK615 has potential as a therapeutic agent for treating inflammatory diseases such as periodontitis. PMID:19706286

  17. Nanoelectronic detection of triggered secretion of pro-inflammatory cytokines using CMOS compatible silicon nanowires.

    Science.gov (United States)

    Pui, Tze-Sian; Agarwal, Ajay; Ye, Feng; Huang, Yinxi; Chen, Peng

    2011-01-15

    Nanotechnology, such as nanoelectronic biosensors, is bringing new opportunities and tools to the studies of cell biology, clinical applications, and drug discovery. In this study, crystalline silicon nanowire based field-effect transistors fabricated using top-down approach were employed to parallelly detect pro-inflammatory cytokines in the complex biological fluids (cell culture medium and blood samples) with high specificity and femtomolar sensitivity. Using this technique, the dynamic secretion of TNF-alpha and IL6 was revealed during the immune response of macrophages and rats to the stimulation of bacteria endotoxin. This technique could provide a unique platform to examine the profile of complex immune responses for fundamental studies and diagnosis. PMID:20977978

  18. Antimicrobial activity of preparation Bioaron C.

    Science.gov (United States)

    Gawron-Gzella, Anne; Michalak, Anna; Kędzia, Anna

    2014-01-01

    The antimicrobial activity of sirupus Bioaron C, a preparation, whose main ingredient is an extract from the leaves of Aloe arborescens, was tested against different microorganisms isolated from patients with upper respiratory tract infections. The experiments were performed on 40 strains: 20 strains of anaerobic bacteria, 13 strains of aerobic bacteria and 7 strains of yeast-like fungi from the genus Candida and on 18 reference strains (ATCC). The antimicrobial activity of Bioaron C (MBC and MFC) was determined at undiluted concentration. Bioaron C proved to be very effective against the microorganisms causing infections. At the concentration recommended by the producer, the preparation showed biocidal activity (MBC, MFC) against the strains of the pathogenic microorganisms, which cause respiratory infections most frequently, including, among others, Peptostreptococcus anaerobius, Parvimonas micra, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus anginosus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa and Candida albicans, already after 15 min. The MIC of Bioaron C against most of the tested microorganisms was 5 to 100 times lower than the usually applied concentration. The great antimicrobial activity means that the preparation may be used in the prevention and treatment of infections of the upper respiratory tract. Bioaron C may be an alternative or complement to classical therapy, especially in children. PMID:25362808

  19. Stop feeding cancer: pro-inflammatory role of visceral adiposity in liver cancer.

    Science.gov (United States)

    Zhao, Jun; Lawless, Matthew W

    2013-12-01

    Liver cancer is the fifth most common cancer in the world with an estimated over half a million new cases diagnosed every year. Due to the difficulty in early diagnosis and lack of treatment options, the prevalence of liver cancer continues to climb with a 5-year survival rate of between 6% and 11%. Coinciding with the rise of liver cancer, the prevalence of obesity has rapidly increased over the past two decades. Evidence from epidemiological studies demonstrates a higher risk of hepatocellular carcinoma (HCC) in obese individuals. Obesity is recognised as a low-grade inflammatory disease, this is of particular relevance as inflammation has been proposed as the seventh hallmark of cancer development with abdominal visceral adiposity considered as an important source of pro-inflammatory stimuli. Emerging evidence points towards the direct role of visceral adipose tissue rather than generalised body fat in carcinogenesis. Cytokines such as IL-6 and TNF-α secreted from visceral adipose tissue have been demonstrated to induce a chronic inflammatory condition predisposing the liver to a protumourigenic milieu. This review focuses on excess visceral adiposity rather than simple obesity; particularly adipokines and their implications for chronic inflammation, lipid accumulation, insulin resistance, Endoplasmic Reticulum (ER) stress and angiogenesis. Evidence of molecular signalling pathways that may give rise to the onset and progression of HCC in this context are depicted. Delineation of the pro-inflammatory role of visceral adiposity in liver cancer and its targeting will provide better rational and therapeutic approaches for HCC prevention and elimination. The concept of a central role for metabolism in cancer is the culmination of an effort that began with one of the 20th century's leading biochemists and Nobel laureate of 1931, Otto Warburg.

  20. Persistent infiltration and pro-inflammatory differentiation of monocytes cause unresolved inflammation in brain arteriovenous malformation.

    Science.gov (United States)

    Zhang, Rui; Han, Zhenying; Degos, Vincent; Shen, Fanxia; Choi, Eun-Jung; Sun, Zhengda; Kang, Shuai; Wong, Michael; Zhu, Wan; Zhan, Lei; Arthur, Helen M; Oh, S Paul; Faughnan, Marie E; Su, Hua

    2016-10-01

    An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes. Mouse bAVM was induced through deletion of AVM causative genes, Endoglin (Eng) globally or Alk1 focally, plus brain focal angiogenic stimulation. An endothelial cell and vascular smooth muscle cell co-culture system was used to analyze monocyte differentiation in the angiogenic niche. After angiogenic stimulation, the Eng-deleted mice had fewer CD68(+) cells at 2 weeks (P = 0.02), similar numbers at 4 weeks (P = 0.97), and more at 8 weeks (P = 0.01) in the brain angiogenic region compared with wild-type (WT) mice. Alk1-deficient mice also had a trend toward more macrophages/microglia 8 weeks (P = 0.064) after angiogenic stimulation and more RFP(+) bone marrow-derived macrophages than WT mice (P = 0.01). More CD34(+) cells isolated from peripheral blood of patients with ENG or ALK1 gene mutation differentiated into macrophages than those from healthy controls (P < 0.001). These data indicate that persistent infiltration and pro-inflammatory differentiation of monocytes might contribute to macrophage accumulation in bAVM. Blocking macrophage homing to bAVM lesions should be tested as a strategy to reduce the severity of bAVM. PMID:27325285

  1. Expression of IP-10 Chemokine is Regulated by Pro-inflammatory Cytokines in Cultured Hepatocytes

    Directory of Open Access Journals (Sweden)

    Gholamhossein Hassanshahi

    2007-09-01

    Full Text Available Chemokines are classified in four distinct groups as CXC, CC, CX3C and C, depending on the presence or absence of a motif called ELR (Arg-Leu-Glu before the first cysteine residue in their structure. CXC chemokines are also subdivided into ELR+ and ELR-. Increasing evidence has indicated the existence of a chemokine network in the liver which is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury.  The CXC chemokines play a major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. The aim of this study was to examine the response of cultured hepatocytes to exogenous inflammatory cytokines (TNF-a and IFN-g regarding expression of IP-10 and growth regulatory oncogen (Gro chemokines. In this study we employed western and northern analysis to measure chemokines at the level of protein and mRNA by hepatocytes in response to pro-inflammatory cytokines. We found that, the pro-inflammatory cytokines, TNF-a and IFN-g, selectively stimulated expression of IP-10 but were without effect on Gro. This confirms a potential direct involvement of these cytokines in chemokine production by hepatocytes. Thus, IFN-g and TNF-a may play a role in hepatic injury and inflammation and produce some of their biological effects by localized induction of chemokines by hepatocytes. Given the similarity to an acute phase response, we were able to show that IFN-g and TNF-a mimicked the effects of cell isolation and culture on induction of IP-10 expression. Further, evidence for linkages between IFN-g and TNF-a and liver injuries is seen in hepatitis C and hepatitis B in which increased levels of TNF-a and its soluble receptor were reported. 

  2. Antimicrobial activity of galls of Quercus infectoria

    OpenAIRE

    Fırat Zafer Mengeloğlu; Umre Metin; Nesibe Özdemir; M. Kadir Oduncu

    2011-01-01

    Objectives: Gall oak (Quercus infectoria) is a species of tree belonging to fagaceae family and its galls has been used in the treatment of burn wounds traditionally. In this study, it is aimed to investigate the antimicrobial activity of the extract of oak galls on some microorganisms.Materials and methods: With using microdilution method, a solution which was obtained by boiling the galls was studied on 20 staphylococci, 20 Pseudomonas aeruginosa and 20 Candida albicans isolates which were ...

  3. Antimicrobial activities of selected Cyathus species.

    Science.gov (United States)

    Liu, Ya-Jun; Zhang, Ke-Qin

    2004-02-01

    Twelve selected Cyathus species were tested for their abilities to produce antimicrobial metabolites. Most of them were found to produce secondary exo-metabolites that could induce morphological abnormalities of rice pathogenic fungi Pyricularia oryzae. Some extracts from the cultivated liquid obviously inhibited human pathogenic fungi Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. Activities against six human pathogenic bacteria were also obtained from some of these extracts. PMID:15119855

  4. Antimicrobial Activity of Indigofera suffruticosa

    OpenAIRE

    Leite, Sônia Pereira; Vieira, Jeymesson Raphael Cardoso; de Medeiros, Paloma Lys; Leite, Roberta Maria Pereira; de Menezes Lima, Vera Lúcia; Xavier, Haroudo Satiro; de Oliveira Lima, Edeltrudes

    2006-01-01

    Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae) obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which showe...

  5. Antimicrobial Activity of Indigofera suffruticosa

    OpenAIRE

    Sônia Pereira Leite; Jeymesson Raphael Cardoso Vieira; Paloma Lys de Medeiros; Roberta Maria Pereira Leite; Vera Lúcia de Menezes Lima; Haroudo Satiro Xavier; Edeltrudes de Oliveira Lima

    2006-01-01

    Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae) obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which sh...

  6. Antimicrobial activity ofGymnema sylvestre (Asclepiadaceae)

    Institute of Scientific and Technical Information of China (English)

    Beverly C. David; G. Sudarsanam

    2013-01-01

    Objective:To evaluate antimicrobial activities of aqueous, methanol, chloroform and hexane extract of leaves plant ofGymnema sylvestre(G. sylvestre).Methods:The antimicrobial screening of the extracts ofG. sylvestre against most prevalent microbes likeStaphylococcus aureus(S. aureus),Bacillus cereus(B. cereus),Klebsiella pneumoniae(K. pneumoniae),Escherichia coli(E. coli),Candida albicans(C. albicans),Candida tropicalis(C. tropicalis),Candida krusei(C. krusei) andCandida kefyr(C. kefyr) by agar well diffusion method, minimum inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration were carried out. Results:The aqueous and methanol leaf extract showed significant antibacterial and antifungal activities against the selected microorganisms when compared to the standard drugs respectively. Conclusions:The dried scale leaves ofG. sylvestre might represent a new antimicrobial source with stable, biologically active components that can establish a scientific base for the use in modern medicine.

  7. Antimicrobial Activity of Indigofera suffruticosa.

    Science.gov (United States)

    Leite, Sônia Pereira; Vieira, Jeymesson Raphael Cardoso; de Medeiros, Paloma Lys; Leite, Roberta Maria Pereira; de Menezes Lima, Vera Lúcia; Xavier, Haroudo Satiro; de Oliveira Lima, Edeltrudes

    2006-06-01

    Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae) obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which showed strong inhibitory activity against the Gram-positive bacteria Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 5000 microg ml(-1). The MIC values to dermatophyte strains were 2500 microg ml(-1) against Trichophyton rubrum (LM-09, LM-13) and Microsporum canis. This study suggests that aqueous extracts of leaves of I. suffruticosa obtained by infusion can be used in the treatment of skin diseases caused by dermatophytes. PMID:16786057

  8. Antimicrobial Activity of Indigofera suffruticosa

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    Sônia Pereira Leite

    2006-01-01

    Full Text Available Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which showed strong inhibitory activity against the Gram-positive bacteria Staphylococcus aureus with a minimal inhibitory concentration (MIC of 5000 µg ml−1. The MIC values to dermatophyte strains were 2500 µg ml−1 against Trichophyton rubrum (LM-09, LM-13 and Microsporum canis. This study suggests that aqueous extracts of leaves of I. suffruticosa obtained by infusion can be used in the treatment of skin diseases caused by dermatophytes.

  9. Antimicrobial Activity of Iberian macroalgae

    OpenAIRE

    Salvador Soler, Noemi; Gómez Garreta, Ma. Amelia; Lavelli, Luca; Ribera Siguán, María Antonia

    2007-01-01

    The antibacterial and antifungal activity of 82 marine macroalgae (18 Chlorophyceae, 25 Phaeophyceae and 39 Rhodophyceae) was studied to evaluate their potential for being used as natural preservatives in the cosmetic industry. The bioactivity was analysed from crude extracts of fresh and lyophilised samples against three Gram-positive bacteria, two Gram-negative bacteria and one yeast using the agar diffusion technique. The samples were collected seasonally from Mediterranean and Atlantic co...

  10. Antimicrobial activity of galls of Quercus infectoria

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    Fırat Zafer Mengeloğlu

    2011-09-01

    Full Text Available Objectives: Gall oak (Quercus infectoria is a species of tree belonging to fagaceae family and its galls has been used in the treatment of burn wounds traditionally. In this study, it is aimed to investigate the antimicrobial activity of the extract of oak galls on some microorganisms.Materials and methods: With using microdilution method, a solution which was obtained by boiling the galls was studied on 20 staphylococci, 20 Pseudomonas aeruginosa and 20 Candida albicans isolates which were obtained from various clinical samples and the values of minimum inhibitor concentration (MIC were detected.Results: At the end of incubation MIC50 and MIC90 values were determined as 0,5 and 1 μg/ml for staphylococci, 1 and 2 μg/ml for Pseudomonas, 2 and 2 μg/ml for Candida, respectively.Conclusion: As a result, we concluded that galls of Q.infectoria has antimicrobial effect on common factors of burn wound infections. Larger studies about the antimicrobial and antiinflamatorial activity and in vivo effect of topical treatment of Q.infectoria will obtain more accurate data about using this plant in the treatment of burn wounds.

  11. Assessing the antimicrobial activities of Ocins.

    Science.gov (United States)

    Choyam, Shilja; Lokesh, Dhanashree; Kempaiah, Bettadaiah Bheemakere; Kammara, Rajagopal

    2015-01-01

    The generation of a zone of inhibition on a solid substrate indicates the bioactivity of antimicrobial peptides such as bacteriocin and enterocin. The indicator strain plays a significant role in bacteriocin assays. Other characteristics of bacteriocins, such as their dispersal ability and the different zymogram components, also affect bacteriocin assays. However, universal well diffusion assays for antimicrobials, irrespective of their ability to diffuse (bacteriocin and enterocin), do not exist. The ability of different zymography components to generate non-specific activities have rarely been explored in the literature. The purpose of the present work was to evaluate the impact of major factors (diffusion and rate of diffusion) in a solid substrate bioassay, and to document the adverse effects of sodium dodecyl sulfate in zymograms used to estimate the approximate molecular weight of bacteriocins. PMID:26441952

  12. Assessing the antimicrobial activities of Ocins

    Directory of Open Access Journals (Sweden)

    Shilja eChoyam

    2015-09-01

    Full Text Available The generation of a zone of inhibition on a solid substrate indicates the bioactivity of antimicrobial peptides such as bacteriocin and enterocin. The indicator strain plays a significant role in bacteriocin assays. Other characteristics of bacteriocins, such as their dispersal ability and the different zymogram components, also affect bacteriocin assays. However, universal well diffusion assays for antimicrobials, irrespective of their ability to diffuse (bacteriocin, enterocin, do not exist. The ability of different zymography components to generate non-specific activities have rarely been explored in the literature. The purpose of the present work was to evaluate the impact of two major factors (diffusion and no diffusion in a solid substrate bioassay, and to document the adverse effects of sodium dodecyl sulfate in zymograms used to estimate the approximate molecular weight of bacteriocins.

  13. Influence of ulinastatin on pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Rui Kang; Jia-Li Xie; Ya-Ni Xue

    2016-01-01

    Objective:To observe the influence of ulinastatin on pulmonary surfactant protein and anti-inflammatory and pro-inflammatory mediator in patients with severe pneumonia. Methods:A total of 54 patients with severe pneumonia treated in our hospital from April 2014 to May 2015 were selected as the study object, and they were randomly divided into control group (conventional treatment of severe pneumonia group) and observation group (conventional treatment and ulinastatin group), with 27 cases in each group. Then the serum levels of pulmonary surfactant protein,anti-inflammatory and pro-inflammatory mediators in two groups before and after treatment at 1 day, 3 day and 5 day were compared. Results:The serum level of pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in two groups before treatment had no significant differences, all P>0.05, and those serum indexes in observation group after treatment at 1 day, 3 day and 5 day were all significantly better than those of the control group, all P<0.05. Conclusions:The ulinastatin can effectively improve the pulmonary surfactant protein, anti-inflammatory and pro-inflammatory mediators in patients with severe pneumonia, and its improvement role for various of severe pneumonia are obvious.

  14. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A

    NARCIS (Netherlands)

    Toelle, Markus; Huang, Tao; Schuchardt, Mirjam; Jankowski, Vera; Pruefer, Nicole; Jankowski, Joachim; Tietge, Uwe J. F.; Zidek, Walter; van der Giet, Markus

    2012-01-01

    Aims High-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end

  15. 2-phenylethynesulfonamide Prevents Induction of Pro-inflammatory Factors and Attenuates LPS-induced Liver Injury by Targeting NHE1-Hsp70 Complex in Mice.

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    Chao Huang

    Full Text Available The endotoxin-mediated production of pro-inflammatory cytokines plays an important role in the pathogenesis of liver disorders. Heat shock protein (Hsp70 overexpression has established functions in lipopolysaccharide (LPS-mediated inflammatory response. However, little is known about the role of Hsp70 activity in LPS signaling. We hypothesized that inhibition of Hsp70 substrate binding activity can ameliorate LPS-induced liver injury by decreasing induction of pro-inflammatory factors. In this study, C57/BL6 mice were injected intraperitoneally with LPS and 2-phenylethynesulfonamide (PES, an inhibitor of Hsp70 substrate binding activity. We found that i. PES prevented LPS-induced increase in serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activity, infiltration of inflammatory cells, and liver cell apoptosis; ii. PES reduced inducible nitric oxide synthase (iNOS protein expression as well as serum nitric oxide (NO, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6 content in LPS-stimulated mice; iii. PES reduced the mRNA level of iNOS, TNF-α, and IL-6 in LPS-stimulated liver. iiii. PES attenuated the degradation of inhibitor of κB-α (IκB-α as well as the phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB in LPS-stimulated liver. Similar changes in the protein expression of inflammatory markers, IκB-α degradation, and NF-κB phosphorylation and nuclear translocation were observed in RAW 264.7 cells. Further mechanistic studies revealed that PES remarkably reduced the elevation of [Ca(2+]i and intracellular pH value (pHi in LPS-stimulated RAW 264.7 cells. Furthermore, PES significantly reduced the increase in Na(+/H(+ exchanger 1 (NHE1 association to Hsp70 in LPS-stimulated macrophages and liver, suggesting that NHE1-Hsp70 interaction is required for the involvement of NHE1 in the inflammation response. In conclusion, inhibition of Hsp70 substrate binding activity in vivo reduces the

  16. ANTIMICROBIAL ACTIVITY OF ALOE VERA LEAF EXTRACT

    OpenAIRE

    Kedarnath; Kamble Kaveri M; Vishwanath B Chimkod; C. S. Patil

    2013-01-01

    The antimicrobial activity of aloe vera extract was tested against pathogenic bacteria like Staphylococcus aureus, Klebisella pneumonia and E.coli and fungi like Aspergillus niger and Candida at a dose of 1:20 mg/ml and 2:40 mg/ml by using cup plate diffusion method. Various solvents such as petroleum ether, chloroform and methanol were used for extracts. The results reveal that, methanol and petroleum ether at a dose of 20 mg/ml has showed significant activity against Klebisella pneumonia an...

  17. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

    Science.gov (United States)

    Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

    2016-09-01

    Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. PMID:27288632

  18. Do mechanical strain and TNF-α interact to amplify pro-inflammatory cytokine production in human annulus fibrosus cells?

    Science.gov (United States)

    Likhitpanichkul, Morakot; Torre, Olivia M; Gruen, Jadry; Walter, Benjamin A; Hecht, Andrew C; Iatridis, James C

    2016-05-01

    During intervertebral disc (IVD) injury and degeneration, annulus fibrosus (AF) cells experience large mechanical strains in a pro-inflammatory milieu. We hypothesized that TNF-α, an initiator of IVD inflammation, modifies AF cell mechanobiology via cytoskeletal changes, and interacts with mechanical strain to enhance pro-inflammatory cytokine production. Human AF cells (N=5, Thompson grades 2-4) were stretched uniaxially on collagen-I coated chambers to 0%, 5% (physiological) or 15% (pathologic) strains at 0.5Hz for 24h under hypoxic conditions with or without TNF-α (10ng/mL). AF cells were treated with anti-TNF-α and anti-IL-6. ELISA assessed IL-1β, IL-6, and IL-8 production and immunocytochemistry measured F-actin, vinculin and α-tubulin in AF cells. TNF-α significantly increased AF cell pro-inflammatory cytokine production compared to basal conditions (IL-1β:2.0±1.4-84.0±77.3, IL-6:10.6±9.9-280.9±214.1, IL-8:23.9±26.0-5125.1±4170.8pg/ml for basal and TNF-α treatment, respectively) as expected, but mechanical strain did not. Pathologic strain in combination with TNF-α increased IL-1β, and IL-8 but not IL-6 production of AF cells. TNF-α treatment altered F-actin and α-tubulin in AF cells, suggestive of altered cytoskeletal stiffness. Anti-TNF-α (infliximab) significantly inhibited pro-inflammatory cytokine production while anti-IL-6 (atlizumab) did not. In conclusion, TNF-α altered AF cell mechanobiology with cytoskeletal remodeling that potentially sensitized AF cells to mechanical strain and increased TNF-α-induced pro-inflammatory cytokine production. Results suggest an interaction between TNF-α and mechanical strain and future mechanistic studies are required to validate these observations.

  19. Selection for genetic variation inducing pro-inflammatory responses under adverse environmental conditions in a Ghanaian population.

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    Maris Kuningas

    Full Text Available BACKGROUND: Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions. METHODOLOGY/PRINCIPAL FINDINGS: In the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p = 0.028 and high TNF-alpha levels (p = 1.39 x 10(-3, was enriched among Ghanaian elders (p = 2.46 x 10(-6. Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes influences mortality risks (HR 1.28, 95% CI [1.09-1.50], we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (p(interaction = 0.013. Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped. CONCLUSIONS/SIGNIFICANCE: Altogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments.

  20. Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines

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    Jantan I

    2014-09-01

    Full Text Available Ibrahim Jantan,1,* Syed Nasir Abbas Bukhari,1,* Olayiwola A Adekoya,2 Ingebrigt Sylte3 1Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Department of Pharmacy, Faculty of Health Science, UiT The Arctic University of Norway, Tromsø, Norway; 3Department of Medical Biology, Faculty of Health Science, UiT The Arctic University of Norway, Tromsø, Norway *These authors contributed equally to this work Abstract: Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A2, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents. Keywords: anti-inflammatory, tumor necrosis factor-alpha, lipopolysaccharides, molecular docking

  1. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

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    Rimbach Gerald

    2011-05-01

    Full Text Available Abstract Background Human paraoxonase 1 (PON1 is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G, a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. Findings To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers. Conclusions Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

  2. S100A12 suppresses pro-inflammatory, but not pro-thrombotic functions of serum amyloid A.

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    Yuen Ming Chung

    Full Text Available S100A12 is elevated in the circulation in patients with chronic inflammatory diseases and recent studies indicate pleiotropic functions. Serum amyloid A induces monocyte cytokines and tissue factor. S100A12 did not stimulate IL-6, IL-8, IL-1β or TNF-α production by human peripheral blood mononuclear cells but low amounts consistently reduced cytokine mRNA and protein levels induced by serum amyloid A, by ∼49% and ∼46%, respectively. However, S100A12 did not affect serum amyloid A-induced monocyte tissue factor. In marked contrast, LPS-induced cytokines or tissue factor were not suppressed by S100A12. S100A12 did not alter cytokine mRNA stability or the cytokine secretory pathway. S100A12 and serum amyloid A did not appear to form complexes and although they may have common receptors, suppression was unlikely via receptor competition. Serum amyloid A induces cytokines via activation of NF-κB and the MAPK pathways. S100A12 reduced serum amyloid A-, but not LPS-induced ERK1/2 phosphorylation to baseline. It did not affect JNK or p38 phosphorylation or the NF-κB pathway. Reduction in ERK1/2 phosphorylation by S100A12 was unlikely due to changes in intracellular reactive oxygen species, Ca(2+ flux or to recruitment of phosphatases. We suggest that S100A12 may modulate sterile inflammation by blunting pro-inflammatory properties of lipid-poor serum amyloid A deposited in chronic lesions where both proteins are elevated as a consequence of macrophage activation.

  3. Pro-inflammatory cytokines and bone fractures in CKD patients. An exploratory single centre study

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    Panuccio Vincenzo

    2012-10-01

    Full Text Available Abstract Background Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients. Methods In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate and inflammatory cytokines (TNF-α, IL-6, CRP. Patients were followed-up until the first non traumatic fracture. Results During follow-up (median: 74 months; range 0.5 -84.0 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95–741 vs 135 pg/ml IQ: 53–346; p = 0.04 and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02. Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03 and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005 predicted bone fractures on univariate Cox’s regression analysis. In restricted (bivariate models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures. Conclusions In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.

  4. Effect of simvastatin on pro-inflammatory cytokines after myocardial in farction in rats

    Institute of Scientific and Technical Information of China (English)

    Jinying Zhang; Yuhua Liao; Xiang Cheng; Baojun Lu

    2005-01-01

    Objective: To study the effect of simvastatin on mRNA expression of inflammatory cytokines, including TNF-α,IL-1β, IL-6, and IL-10, after myocardial infarction (MI) in rats. Methods: The experimental rats were divided into three groups: Sham operation group (Sham), the rats were performed a left thoracotomy with no ligation of left descending coronary artery (LAD); Myocardial infarction control group (MI-C), the rats were performed a left thoracotomy with ligation of LAD; Simvastatin group (MI-S), the rats were performed a left thoracotomy with ligation of LAD, and given simvastatin 40 mg/kg body weight per day through gavage, while the other two groups were given equal normal saline by gavage. All animals were caged to feed four weeks. After finished, the rats were killed, and the hearts were harvested and cut into two equal parts at the level of the papillary muscle: one was used to determine mRNA expression of myocardial cytokines by RT-PCR, and the other was used to measure cytokines by Western blotting and immunohistochemical staining. Results: All the pro-inflammatory cytokines mentioned above showed few expression in Sham operation group. In the MI groups(including MI-C and MI-S groups), mRNA expression of each of these cytokines markedly increased compared with the Sham operation group ( P < 0.01). Compared with MI-C group, the mRNA expression of TNF-α, IL-1β and IL-6 in the MI-S group significantly reduced( P < 0.01), and mRNA expression of IL-10 obviously increased ( P < 0.01). Cytokines principally located in cardiomyocytes of non-infarcted area and survived cardiomyocytes of infarcted area, simvastatin could decrease TNF-α, IL-1β, and IL-6 and increase IL-10 by confirmation of immunohistochemical staining. Conclusion: Simvastatin markedly lowers pro-inflammatory cytokines, and increases inflammatory protective cytokine. Its mechanism needs to be elucidated.

  5. ANTIMICROBIAL ACTIVITY OF TUSSILAGO FARFARA L.

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    Miroslava Kačániová

    2013-02-01

    Full Text Available In this study, ethanolic extracts of Tussilago farfara L. which had been described in herbal books, were screened for their antimicrobial activity. The following strains of bacteria for antimicrobial activity were used Escherichia coli CCM 3988, Serratia rubidea CCM 4684, Staphylococcus epidermis CC 4418, Lactobacillus rhamnosus CCM 1828, Pseudomonas aeroginosa CCM 1960 and Enterococcus raffinosus CCM 4216. The yeast strain used in this study was Saccharomyces cerevisiae CCM 8191 using disc diffusion method and microbroth dilution technique. The highest antibacterial activity of Tussilago farfara L. ethanolic extract was measured in Grampositive bacteria Lactobacillus rhamnosus (6.67±1.53 mm and lower in yeast Saccharomyces cerevisiae (1.67±0.58 mm with disc diffusion method used. The ethanolic extract present an important activity against Saccharomyces cerevisiae (MIC50=24 µg.ml-1; MIC90=25.69 µg.ml-1 and Serratia rubidaea (MIC=48.01 µg.ml-1; MIC90=51.26 µg.ml-1 with microbroth dilution technique used.

  6. Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7)

    Institute of Scientific and Technical Information of China (English)

    Rajendra Karki; Cheol-Ho Park; Dong-Wook Kim

    2013-01-01

    OBJECTIVE:Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs.The purpose of this study was to evaluate the effects of tartary buckwheat (Fagopyrum tataricum) sprouts on oxidation and pro-inflammatory mediators.METHODS:The anti-oxidant effects of buckwheat extract (BWE) and rutin were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH)-and nitric oxide (NO)-scavenging activities,serum peroxidation and chelating assays.Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of buckwheat and rutin.NO production in LPS-stimulated RAW264.7 cells was determined by using Griess reagent.The expressions of inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2),nuclear factor-kappa B (NF-κB) p65 subunit in cytosolic and nuclear portions were determined by Western blot analysis.Also,the production of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay.RESULTS:Inhibitory concentration 50 values for DPPH-and NO-scavenging activities of BWE were 24.97 and 72.54 μg/mL respectively.BWE inhibited serum oxidation and possessed chelating activity.Furthermore,BWE inhibited IL-6 and TNF-α production in LPS-stimulated RAW264.7 cells.Also,BWE inhibited iNOS and COX-2 expression and NF-κB p65 translocation.CONCLUSION:Buckwheat sprouts possessed strong antioxidant activity and inhibited production of pro-inflammatory mediators in the applied model systems.Thus,buckwheat can be suggested to be beneficial in inflammatory diseases by inhibiting the free radicals and inflammatory mediators.

  7. Potential Effects of Pomegranate on Lipid Peroxidation and Pro-inflammatory Changes in Daunorubicin-induced Cardiotoxicity in Rats

    Science.gov (United States)

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Daunorubicin-induced acute cardiotoxicity caused by oxidative stress and free radical formation. Pomegranate possessed a significant in vitro free radical scavenging activity. Therefore, the aim of this study was estimations of the role of pomegranate effects in daunorubicin-induced cardiotoxicity. Methods: A total of 21 Sprague male rats were allocated into three groups, seven animals in each group. Group A: Control group received distilled water. Group B: Treated group with daunorubicin 20 mg/kg via intraperitoneal injection daily for the 12th day for total cumulative dose of 240 mg/kg. Group C: Pretreatment group with pomegranate 25 mg/kg for 6 days orally, then daunorubicin 20 mg/kg administrated concomitantly for the next 6 days with a cumulative dose of 120 mg/kg. Cardiac troponin I([cTn I] pg/ml), malondialdehyde (MDA) (ng/ml), interleukin 17 (IL-17 pg/ml), and cardiac lactate dehydrogenase (LDH) (pm/ml), all these biomarkers were used to measure the severity of cardiotoxicity. Results: Daunorubicin at a dose of 20 mg/kg lead to pronounced cardiac damage that reflected on through elevations of serum cTn and serum LDH levels significantly P Pomegranate pretreatment demonstrated a significant cardioprotection from daunorubicin-induced cardiotoxicity; it attenuated the cardiac damage through reduction of cTn, LDH, MDA, and serum IL-17 level significantly P Pomegranate demonstrated significant cardioprotection in daunorubicin-induced cardiotoxicity through reduction of oxidative stress, lipid peroxidation, pro-inflammatory, and cardiac injury biomarkers. PMID:27413516

  8. Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages.

    Science.gov (United States)

    Shaw, Catherine A; Mortimer, Gysell M; Deng, Zhou J; Carter, Edwin S; Connell, Shea P; Miller, Mark R; Duffin, Rodger; Newby, David E; Hadoke, Patrick W F; Minchin, Rodney F

    2016-09-01

    In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages. All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720 ± 850 pg/mL to 5560 ± 1380 pg/mL (p = 0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung. PMID:27027807

  9. Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.

    Science.gov (United States)

    Mata, Mariana M; Napier, T Celeste; Graves, Steven M; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L

    2015-04-01

    The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.

  10. Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages.

    Science.gov (United States)

    Shaw, Catherine A; Mortimer, Gysell M; Deng, Zhou J; Carter, Edwin S; Connell, Shea P; Miller, Mark R; Duffin, Rodger; Newby, David E; Hadoke, Patrick W F; Minchin, Rodney F

    2016-09-01

    In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages. All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720 ± 850 pg/mL to 5560 ± 1380 pg/mL (p = 0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung.

  11. Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques.

    Science.gov (United States)

    Shalhoub, Joseph; Viiri, Leena E; Cross, Amanda J; Gregan, Scott M; Allin, David M; Astola, Nagore; Franklin, Ian J; Davies, Alun H; Monaco, Claudia

    2016-05-01

    Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours. Supernatants were interrogated for 45 analytes using the Luminex 100 platform. Twenty-nine of the 45 analytes were reproducibly detectable in the majority of donors. The in vitro production of a specific network of mediators was found to be significantly higher in symptomatic than asymptomatic plaques, including: tumour necrosis factor α, interleukin (IL) 1β, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), CCL5, CCL20, CXCL9, matrix metalloproteinase (MMP)-3 and MMP-9. Ingenuity pathway analysis of differentially expressed analytes between symptomatic and asymptomatic patients identified a number of key biological pathways (p< 10(-25)). In conclusion, the carotid artery plaque culprit of ischaemic neurological symptoms is characterised by an inflammatory milieu favouring inflammatory cell recruitment and pro-inflammatory macrophage polarisation. PMID:26763091

  12. Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing.

    Science.gov (United States)

    Schaafsma, W; Zhang, X; van Zomeren, K C; Jacobs, S; Georgieva, P B; Wolf, S A; Kettenmann, H; Janova, H; Saiepour, N; Hanisch, U-K; Meerlo, P; van den Elsen, P J; Brouwer, N; Boddeke, H W G M; Eggen, B J L

    2015-08-01

    Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1mg/kg) or intracerebroventricular (5 μg) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-1β and TNF-α genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1β promoter. ChIP and knock-down experiments showed that NF-κB subunit RelB was bound to the IL-1β promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation.

  13. Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation.

    Science.gov (United States)

    Jacques, Carlos Eduardo Diaz; Donida, Bruna; Mescka, Caroline P; Rodrigues, Daiane G B; Marchetti, Desirèe P; Bitencourt, Fernanda H; Burin, Maira G; de Souza, Carolina F M; Giugliani, Roberto; Vargas, Carmen Regla

    2016-09-01

    Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients. Thus, the aim of this study was to investigate oxidative, nitrative and inflammatory biomarkers in MPS II patients submitted to long term ERT. It were analyzed urine and blood samples from patients on ERT (mean time: 5.2years) and healthy controls. Patients presented increased levels of lipid peroxidation, assessed by urinary 15-F2t-isoprostane and plasmatic thiobarbituric acid-reactive substances. Concerning to protein damage, urinary di-tyrosine (di-Tyr) was increased in patients; however, sulfhydryl and carbonyl groups in plasma were not altered. It were also verified increased levels of urinary nitrate+nitrite and plasmatic nitric oxide (NO) in MPS II patients. Pro-inflammatory cytokines IL-1β and TNF-α were increased in treated patients. GAG levels were correlated to di-Tyr and nitrate+nitrite. Furthermore, IL-1β was positively correlated with TNF-α and NO. Contrastingly, we did not observed alterations in erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, in reduced glutathione content and in the plasmatic antioxidant capacity. Although some parameters were still altered in MPS II patients, these results may suggest a protective role of long-term ERT against oxidative stress, especially upon oxidative damage to protein and enzymatic and non-enzymatic defenses. Moreover, the redox imbalance observed in treated patients seems to be GAG- and pro-inflammatory cytokine-related. PMID:27251652

  14. Quaternized Chitosan as an Antimicrobial Agent: Antimicrobial Activity, Mechanism of Action and Biomedical Applications in Orthopedics

    Directory of Open Access Journals (Sweden)

    Ziwei Liu

    2013-01-01

    Full Text Available Chitosan (CS is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral or high pH substantially limits its use. Quaternary ammonium CS, which was prepared by introducing a quaternary ammonium group on a dissociative hydroxyl group or amino group of the CS, exhibited improved water solubility and stronger antibacterial activity relative to CS over an entire range of pH values; thus, this quaternary modification increases the potential biomedical applications of CS in the field of anti-infection. This review discusses the current findings on the antimicrobial properties of quaternized CS synthesized using different methods and the mechanisms of its antimicrobial actions. The potential antimicrobial applications in the orthopedic field and perspectives regarding future studies in this field are also considered.

  15. Extracts of brown seaweeds can attenuate the bacterial lipopolysaccharide-induced pro-inflammatory response in the porcine colon ex vivo.

    Science.gov (United States)

    Bahar, B; O'Doherty, J V; Hayes, M; Sweeney, T

    2012-12-01

    Bioactive compound-rich brown seaweeds are demonstrated to have numerous health benefits including anti-microbial and immunomodulatory bioactivities in the pig intestine. In this study, the immunomodulating effects of extracts of brown seaweed (Ascophyllum nodosum and Fucus serratus) were evaluated on the porcine colon using a bacterial lipopolysaccharide (LPS) ex vivo model. Approximately 1.5 × 1.5 cm of pig colon (n = 6) was stripped of its overlying muscle layer and incubated in 1 mL Dulbecco's Modified Eagle Medium containing bacterial LPS (10 μg) and seaweed extracts (1 mg). Gene expression of interleukin-8 (IL-8) and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFA) were measured using quantitative real time PCR. In contrast to the low level of expression of IL-8, IL-6, and TNFA genes in the colonic tissue at 0 h, LPS treatment increased (P Ascophyllum. Ascophyllum extract reduced (P Ascophyllum and Fucus seaweeds have potential to suppress the pro-inflammatory response induced by the bacterial LPS in the pig colon. PMID:23365280

  16. Synergistic effect of simvastatin and ezetimibe on lipid and pro-inflammatory profiles in pre-diabetic subjects

    OpenAIRE

    Kater Ana-Lucia A; Batista Marcelo C; Ferreira Sandra RG

    2010-01-01

    Abstract Background Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial. Objective This open-label trial evaluated whether the combination of simvastatin and ezetimibe also results in a synergistic effect that reduces the pro-inflammatory status of pre-diabetic subjects. Methods Fifty pr...

  17. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria

    OpenAIRE

    Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

    2013-01-01

    Objective. Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. Methods. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had prev...

  18. Antimicrobial activity of human salivary mucin-derived peptides

    NARCIS (Netherlands)

    Wei, G.

    2008-01-01

    We investigated: a) relationships between molecular properties and antimicrobial functions of MUC7 peptides, b) effects of host physiological factors on the antimicrobial activity of MUC7 peptides, c) enhancement of antifungal activity by combination of MUC7 peptides with EDTA or other agents, d) an

  19. Both common and specialty mushrooms inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells in a pro-inflammatory environment

    Directory of Open Access Journals (Sweden)

    Martin Keith R

    2010-07-01

    Full Text Available Abstract Background Cardiovascular disease (CVD is a leading cause of mortality in the United States as well as globally. Epidemiological studies show that regular fruit and vegetable consumption reduces CVD risk, in part, due to antioxidant activity and immunomodulation since oxidative stress and inflammation are features of atherogenesis. Accumulating evidence also shows that dietary fungi, viz., mushrooms, can protect against chronic disease by altering inflammatory environments such as those associated with CVD although most research has focused on specialty mushrooms. In this study, we tested the ability of both common and specialty mushrooms to inhibit cellular processes associated with CVD. Methods Human aortic endothelial cells (HAEC were incubated overnight with control media with dimethylsulfoxide (DMSO vehicle (1% v/v or containing DMSO extracts of whole dehydrated mushrooms (0.1 mg/mL, which included Agaricus bisporus (white button and crimini, Lentinula edodes (shiitake, Pleurotus ostreatus (oyster, and Grifola frondosa (maitake. Monolayers were subsequently washed and incubated with medium alone or containing the pro-inflammatory cytokine IL-1β (5 ng/mL for 6 h to upregulate pro-atherosclerotic adhesion molecules (AM. AM expression was assayed by ELISA and binding of U937 human monocytes pre-loaded with fluorescent dye was determined. Results White button mushrooms consistently reduced (p Conclusion These data provide evidence that dietary mushrooms can inhibit cellular processes such as adhesion molecule expression and ultimate binding of monocytes to the endothelium under pro-inflammatory conditions, which are associated with CVD. As a result, these findings support the notion that dietary mushrooms can be protective against CVD.

  20. Maternal Supplementation with Oligofructose (10%) during Pregnancy and Lactation Leads to Increased Pro-Inflammatory Status of the 21-D-Old Offspring

    Science.gov (United States)

    Mennitti, Laís Vales; Oyama, Lila Missae; de Oliveira, Juliana Lopez; Hachul, Ana Claudia Losinskas; Santamarina, Aline Boveto; de Santana, Aline Alves; Okuda, Marcos Hiromu; Ribeiro, Eliane Beraldi; Oller do Nascimento, Claudia Maria da Penha; Pisani, Luciana Pellegrini

    2015-01-01

    Previously, we showed that oligofructose (10%) supplementation during pregnancy and lactation increased endotoxemia in 21-d-old pups. The present study evaluated the effect of 10% oligofructose diet supplementation during pregnancy and lactation in the presence or absence of hydrogenated vegetable fat on the pro-inflammatory status of 21-d-old offspring. On the first day of pregnancy, female Wistar rats were divided into the following groups: control diet (C), control diet supplemented with 10% oligofructose (CF), diet enriched with hydrogenated vegetable fat (T) or diet enriched with hydrogenated vegetable fat supplemented with 10% oligofructose (TF). Diets were maintained during pregnancy and lactation. Serum TNF-α (tumor necrosis factor alpha) was assessed using a specific kit. Protein expression was determined by Western Blotting, and the relative mRNA levels were analyzed by RT-PCR (real-time polymerase chain reaction). We observed that 10% oligofructose supplementation during pregnancy and lactation increased offspring’s IL-6R (interleukin-6 receptor) mRNA levels in the liver and RET (retroperitoneal white adipose tissue) and decreased ADIPOR2 (adiponectin receptor 2) and ADIPOR1 (adiponectin receptor 1) gene expression in liver and EDL (extensor digital longus)/ SOL (soleus) muscles of CF group. Additionally, TF group presented with increased serum TNF-α, protein expression of p-NFκBp65 (phosphorylated form of nuclear factor kappa B p65 subunit) in liver and IL-6R mRNA levels in RET. These findings were accompanied by decreased levels of ADIPOR1 mRNA in the EDL and SOL muscles of the TF group. In conclusion, supplementing the dam’s diet with 10% of oligofructose during pregnancy and lactation, independent of hydrogenated vegetable fat addition, contributes to the increased pro-inflammatory status of 21-d-old offspring, possibly through the activation of the TLR4 (toll like receptor 4) pathway. PMID:26147005

  1. Serum levels of the pro-inflammatory cytokine interleukin-12 and the anti-inflammatory cytokine interleukin-10 in patients with psoriasis treated by the Goeckerman regimen

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Andrys, C.; Krejsek, J.; Hamakova, K.; Kremlacek, J.; Ettler, K.; Fiala, Z. [Charles University Prague, Hradec Kralove (Czech Republic)

    2008-08-15

    The Goeckerman regimen (GR) involves the dermal application of a crude coal tar (polycyclic aromatic hydrocarbon, PAH) and exposure to ultraviolet (UV) radiation. Both PAH and UV radiation exhibit immunosuppressive activity. This study describes the changes in the serum levels of the pro-inflammatory cytokine interleukin-12 (IL-12) and the anti-inflammatory cytokine IL-10 in patients with psoriasis (n = 55) treated with GR. The serum levels of IL-12 and IL-10 were compared before and after GR. In addition, the IL-12 and IL-10 levels in psoriatic patients were compared with those in a control group of healthy blood donors (n = 47). The Psoriasis Area and Severity Index (PASI) was used to evaluate the efficacy of GR. When compared with the control group, both IL-12 and IL-10 were significantly higher in psoriatic patients in all cases (P < 0.001). When compared before and after GR, the IL-12 and IL-10 levels (P < 0.01) and PASI value (P < 0.001) were significantly lower after GR. The decrease in the serum level of IL-12 and IL-10 after GR was related to the entry value before GR (IL-12, r = 0.60, P < 0.001; IL-10, r = 0.36, P < 0.01). There was a significant correlation between the IL-10 level before GR and the PASI value after GR = -0.39; P < 0.01). The results indicate a strong pro-inflammatory effect of IL-12 in the immunopathogenesis of psoriasis, and confirm the immunosuppressive and anti-inflammatory effect of GR. IL-10 seems to be a promising individual marker for a positive effect of GR therapy.

  2. Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner.

    Science.gov (United States)

    Kawano, Yoshinaga; Nakae, Jun; Watanabe, Nobuyuki; Kikuchi, Tetsuhiro; Tateya, Sanshiro; Tamori, Yoshikazu; Kaneko, Mari; Abe, Takaya; Onodera, Masafumi; Itoh, Hiroshi

    2016-08-01

    High-fat diet (HFD) induces low-grade chronic inflammation and insulin resistance. However, little is known about the mechanism underlying HFD-induced chronic inflammation in peripheral insulin-responsive tissues. Here, we show that colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD conditions. To investigate the pathophysiological role of colonic macrophages, we generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M-Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout (Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory macrophages, decreased intestinal permeability, and inactivation of the colonic inflammasome. Interestingly, they showed significantly improved glucose tolerance and insulin sensitivity with decreased chronic inflammation of adipose tissue. Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD-induced insulin resistance and could be a novel therapeutic approach for type 2 diabetes. PMID:27508875

  3. Naegleria fowleri lysate induces strong cytopathic effects and pro-inflammatory cytokine release in rat microglial cells.

    Science.gov (United States)

    Lee, Yang-Jin; Park, Chang-Eun; Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jinyoung; Jung, Suk-Yul; Shin, Ho-Joon

    2011-09-01

    Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A (51)Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.

  4. Naegleria fowleri Lysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells

    Science.gov (United States)

    Lee, Yang-Jin; Park, Chang-Eun; Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jinyoung; Jung, Suk-Yul

    2011-01-01

    Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response. PMID:22072830

  5. Ubiquinol decreases monocytic expression and DNA methylation of the pro-inflammatory chemokine ligand 2 gene in humans

    Directory of Open Access Journals (Sweden)

    Fischer Alexandra

    2012-10-01

    Full Text Available Abstract Background Coenzyme Q10 is an essential cofactor in the respiratory chain and serves in its reduced form, ubiquinol, as a potent antioxidant. Studies in vitro and in vivo provide evidence that ubiquinol reduces inflammatory processes via gene expression. Here we investigate the putative link between expression and DNA methylation of ubiquinol sensitive genes in monocytes obtained from human volunteers supplemented with 150 mg/ day ubiquinol for 14 days. Findings Ubiquinol decreases the expression of the pro-inflammatory chemokine (C-X-C motif ligand 2 gene (CXCL2 more than 10-fold. Bisulfite-/ MALDI-TOF-based analysis of regulatory regions of the CXCL2 gene identified six adjacent CpG islands which showed a 3.4-fold decrease of methylation status after ubiquinol supplementation. This effect seems to be rather gene specific, because ubiquinol reduced the expression of two other pro-inflammatory genes (PMAIP1, MMD without changing the methylation pattern of the respective gene. Conclusion In conclusion, ubiquinol decreases monocytic expression and DNA methylation of the pro-inflammatory CXCL2 gene in humans. Current Controlled Trials ISRCTN26780329.

  6. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    Science.gov (United States)

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  7. Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro

    International Nuclear Information System (INIS)

    Epidemiological studies have consistently reported a higher incidence of respiratory illnesses such as bronchitis, metal fume fever (MFF), and chronic pneumonitis among welders exposed to high concentrations of metal-enriched welding fumes. Here, we studied the molecular toxicology of three different metal-rich welding fumes: NIMROD 182, NIMROD c276, and COBSTEL 6. Fume toxicity in vitro was determined by exposing human type II alveolar epithelial cell line (A549) to whole welding fume, a soluble extract of fume or the 'washed' particulate. All whole fumes were significantly toxic to A549 cells at doses >63 μg ml-1 (TD 50; 42, 25, and 12 μg ml-1, respectively). NIMROD c276 and COBSTEL 6 fumes increased levels of IL-8 mRNA and protein at 6 h and protein at 24 h, as did the soluble fraction alone, whereas metal chelation of the soluble fraction using chelex beads attenuated the effect. The soluble fraction of all three fumes caused a rapid depletion in intracellular glutathione following 2-h exposure with a rebound increase by 24 h. In addition, both nickel based fumes, NIMROD 182 and NIMROD c276, induced significant reactive oxygen species (ROS) production in A549 cells after 2 h as determined by DCFH fluorescence. ICP analysis confirmed that transition metal concentrations were similar in the whole and soluble fractions of each fume (dominated by Cr), but significantly less in both the washed particles and chelated fractions. These results support the hypothesis that the enhanced pro-inflammatory responses of welding fume particulates are mediated by soluble transition metal components via an oxidative stress mechanism

  8. Pro-inflammatory cytokines profiles in Nigerian pregnant women infected withPlasmodium falciparum malaria

    Institute of Scientific and Technical Information of China (English)

    Nmorsi OPG; Isaac C; Ohaneme BA; Obiazi HAK

    2010-01-01

    Objective:To investigate the pro-inflammatory cytokines profiles in in Nigerian pregnant women infected withPlasmodium falciparum (P. falciparum) malaria.Methods: Peripheral, and placental blood samples were collected from96 consenting volunteers comprising76 P. falciparium infected pregnant women and 20 healthy uninfected pregnant women in Ekpoma, Nigeria, and subjected to ELISA for cytokines evaluation.Results: Increased serum concentrations of interferon-gamma(IFN-γ) was observed in infected pregnant women than their uninfected counterparts[(31.2±20.9)pg/mL vs (1.8±0.9) pg/mL] and these differences were statistically significant(″2= 26.18,P0.05). The interleukin-6 (IL-6) was significantly elevated in infected pregnant women (81.0±26.1 pg/mL) than in the uninfected pregnant women [(25.0±5.0) pg/mL](″2 = 29.58,P<0.05). In all, mean cytokines concentration of IL-6, IL-12 andIFN-γ in the placental blood from infected pregnant women were (53.5±23.4) pg/mL, (8.7±6.9) pg/mL and(16.4±4.0) pg/mL, respectively. The multigravidae had a higher haemoglobin level of 10.2 g/dL and birth weight of3 000 g than the primigrivadae with lower haemoglobin level of7.5g/dL and birth weight of2 430 g. Conclusions: The elevatedIFN-γamong the malarous pregnant women implicates it as the major cytokine mediator in the host responses to systematicP. falciparummalaria in our locality.

  9. Antimicrobial Activity of Protamine against Oral Microorganisms.

    Science.gov (United States)

    Kim, Yeon-Hee; Kim, Sang Moo; Lee, Si Young

    2015-01-01

    Protamine is an arginine-rich polycationic protein extracted from sperm cells of vertebrates including fishes such as salmon. The purpose of this study was to investigate the suppressive effects of protamine on the growth of oral pathogens for possible usage in dental materials. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by the microdilution method. Twelve strains of oral viridans streptococci, Actinomyces naeslundii, Actinomyces odontolyticus, Enterococcus faecalis, Lactobacillus acidophilus, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans were suppressed by protamine. MIC and MBC values were between 0.009 ~ 20 mg/mL and 0.019 ~ 80 mg/mL, respectively. The bactericidal activities of protamine against susceptible bacterial species were dependent on the concentration of protamine and incubation time. Based on the results of this study, protamine would be a useful compound for the development of antimicrobial agents against oral pathogens in dental materials. PMID:26699859

  10. Evaluation of Antimicrobial Activity of Root Extracts of Abitulon indicum

    Directory of Open Access Journals (Sweden)

    Krishna Rao MORTHA

    2015-06-01

    Full Text Available Antimicrobial activity of Abitulon indicum roots was studied against seven pathogenic bacteria and three fungal strains by agar well diffusion method. Antimicrobial activity was recorded for hexane, chloroform, methanol, ethanol and aqueous extracts. Alcohol (ethanol and methanol extracts exhibited the highest degree of antimicrobial activity compared to aqueous, chloroform and hexane extracts. Pseudomonas aeruginosa was turned out to be the most susceptible bacterium to the crude root chemical constituents, using the standard Tetracycline and Clotrimazole. Minimum inhibition concentration values of hexane, chloroform, methanol, ethanol and aqueous extracts were determined by the agar dilution method and ranged between 62.5 and 1,000 µg. The study suggested that the root extracts possess bioactive compounds with antimicrobial activity against the tested bacteria and fungi, revealing a significant scope to develop a novel broad spectrum of antimicrobial drug formulation from Abitulon indicum.

  11. ANTIMICROBIAL ACTIVITY OF ALOE VERA LEAF EXTRACT

    Directory of Open Access Journals (Sweden)

    Kedarnath

    2013-12-01

    Full Text Available The antimicrobial activity of aloe vera extract was tested against pathogenic bacteria like Staphylococcus aureus, Klebisella pneumonia and E.coli and fungi like Aspergillus niger and Candida at a dose of 1:20 mg/ml and 2:40 mg/ml by using cup plate diffusion method. Various solvents such as petroleum ether, chloroform and methanol were used for extracts. The results reveal that, methanol and petroleum ether at a dose of 20 mg/ml has showed significant activity against Klebisella pneumonia and E.coli whereas in fungi, methanol extract showed significant activity against Aspergillus niger and Candida. Methanol extract has showed maximum inhibitory activity against E.coli and Candida. Petroleum ether has showed moderate inhibitory activity against Klebisella pneumonia and Candida. The zone of inhibition was measured and compared with standard Gentamycin (1 mg/ml. However, in none of the above mentioned extracts the inhibition zone was not more than that found in standard i.e., Gentamycin.

  12. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Directory of Open Access Journals (Sweden)

    Shunying Jin

    Full Text Available Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC deposition-induced acute lung injury (ALI. Components of gamma amino butyric acid (GABA signaling, including GABA B receptor 2 (GABABR2, GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP, in the bronchoalveolar lavage fluid (BALF. Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting

  13. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    Science.gov (United States)

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  14. Antimicrobial activity of peppermint essential oil (Mentha piperita L.

    Directory of Open Access Journals (Sweden)

    Shapoval O.G.

    2011-12-01

    Full Text Available Рurposе. To study antimicrobial activity of fume of the essential oil of peppermint against gram-positive and gram-negative bacteria. Materials and methods: The screening study of antimicrobial activity of solutions of essential oil by disk-diffusion method and activity of essential oil fume of own preparation and pharmaceutical form of oil according to standard strains of Staphylococcus aureus, Pseudomonas aeruginosa, Esсherichia coli and 12 clinical strains of staphylococci (6 methicillin-resistant and 6 methicillin-sensitive has been carried out. Results: Essential oil of own preparation and pharmaceutical form showed equal antimicrobial activity against strains of staphylococci. Essential oil of own preparation has been determined to reveal higher activity against gram-negative strains. Conclusion: Received data have proved the presence of antimicrobial activity against all strains of microorganisms and mostly against staphy-lococci

  15. ANTIMICROBIAL ACTIVITIES OF 1,3,4-OXADIAZOLE : A REVIEW

    Directory of Open Access Journals (Sweden)

    Bachwani Mukesh

    2011-06-01

    Full Text Available 1, 3, 4-Oxadiazole is a highly privileged structure the derivatives of which exhibit a wide range of biological activities including antibacterial, antitubercular, vasodialatory, antifungal, cytotoxic, anti-inflammatory and analgesic, hypolipidemic, anticancer and ulcerogenic activities. Resistance to number of antimicrobial agents among a variety of clinically significant species of bacteria is becoming increasingly important global problem. The search for new antimicrobial agents will consequently always remain as an important and challenging task for medicinal chemists. This Review has basic information about 1,3,4-oxadiazole and its antimicrobial activity work for further development in this field.

  16. Antimicrobial activity of peppermint essential oil (Mentha piperita L.)

    OpenAIRE

    Shapoval O.G.; Durnova N.A.; Shub G.M.; Golikov A.G.; Raikova S.V.; Rakhmetova A.Yu.

    2011-01-01

    Рurposе. To study antimicrobial activity of fume of the essential oil of peppermint against gram-positive and gram-negative bacteria. Materials and methods: The screening study of antimicrobial activity of solutions of essential oil by disk-diffusion method and activity of essential oil fume of own preparation and pharmaceutical form of oil according to standard strains of Staphylococcus aureus, Pseudomonas aeruginosa, Esсherichia coli and 12 clinical strains of staphylococci (6 methicillin-r...

  17. ANTIMICROBIAL ACTIVITY OF CLEMATIS BRACHIATA THUNB LEAF EXTRACTS

    OpenAIRE

    M. Mostafa* and A.J. Afolayan

    2013-01-01

    The antimicrobial activity as well as phytochemical screening of the hexane, acetone, methanol and water extracts of Clematis brachiata Thunb (Ranunculaceae) leaves was investigated. The agar dilution assay method was used for the evaluation of the antimicrobial activity of extracts against 10 bacteria and four fungal species. The phytochemical screenings were performed by using the standard procedures. The acetone and methanol extracts were active against the 10 bacteria strains with MIC ran...

  18. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.

    Science.gov (United States)

    Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

    2015-07-01

    Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

  19. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.

    Science.gov (United States)

    Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

    2015-07-01

    Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics.

  20. Antimicrobial Activity of Bee Collected Pollen against Clostridia

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    Miroslava Kačániová

    2014-11-01

    Full Text Available Clostridium is an anaerobic, endospore forming Gram-positive bacillus genus containing many important pathogenic species. Many naturally occurring compounds present in plants, herbs, and spices have been shown to possess antimicrobial effect against foodborne pathogens. In the present study, the antimicrobial activities of the bee collected pollen samples were investigated. The antimicrobial activities were determined by using agar disc diffusion method against Clostridium genus. Antibacterial activity was assessed on the clostridia: Clostridium butyricum, Clostridium hystoliticum, Clostridium intestinale, Clostridium perfringens and Clostridium ramosum. The results of the disk diffusion method showed very different activity against all tested strains of clostridia. The best antimicrobial activity of bee collected pollen against C. butyricum and C. perfringens were found.

  1. Antioxidant and antimicrobial activities of Saraca thaipingensis Cantley ex Prain

    Institute of Scientific and Technical Information of China (English)

    Supaluk Prachayasittikul; Apilak Worachartcheewan; Sakda Yainoy; Natthakaln Lomchoey; Paveena Kittiphatcharin; Somsak Ruchirawat; Virapong Prachayasittikul

    2012-01-01

    Objective: To investigate antioxidant and antimicrobial activities of Saraca thaipingensis Cantley ex Prain; and isolation of its flower extracts. Methods: The plant species (flowers, leaves, and twigs) were extracted by hexane, dichloromethane, ethyl acetate and methanol; and tested for antioxidant activity (DPPH assay) and antimicrobial activity (agar dilution method) against twenty-seven strains of microorganisms; gram positive and gram negative bacteria, and diploid fungus. Bioactive constituents were isolated by column chromatography. Results: The plant extracts has been firstly reported to display strong antioxidant activity and antimicrobial activity selective against gram positive bacteria (Corynebacterium diphtheriae NCTC 10356 and Streptococcus pyogenes) with MIC of 256 μg/mL. Stigmasterol and a mixture of triterpenoids and phenolic compounds were isolated from the flower extracts. Conclusions: The study revealed that the S. thaipingensis is a new source of natural antioxidants and antimicrobials with potential for medicinal uses.

  2. Screening of some Malay medicated oils for antimicrobial activity

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    Khalid Khalisanni

    2010-01-01

    Full Text Available Oils from six Malay medicated oils, used traditionally in the treatment of infectious and septic diseases in humans, were tested for their antimicrobial property. The aim was to evaluate the antimicrobial properties of six Malay medicated oils against certain microbial isolates. Locally available Malay medicated oils were checked for their antimicrobial activities using six species of bacteria: E. coli, Salmonella spp., Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus, Bacillus subtilis and 2 fungi with 1 yeast (Aspergillus niger, Penicillum spp. and Candida albicans. Clove oil showed the highest antibacterial activity followed, respectively, by 'bunga merah', cajaput, nutmeg, lemon grass and 'gamat' oil. Clove oil and lemon grass showed anticandidal activity. The Malay medicated oil studies did not show any antifungal activity. The study shows that Malay medicated oils, like antibiotics, have antimicrobial activities against some microorganisms.

  3. Antimicrobial activity of UMFix tissue fixative

    OpenAIRE

    Cleary, T J; Morales, A. R.; Nadji, M.; Nassiri, M.; Vincek, V.

    2005-01-01

    Aims: The aim of this study was to determine the antimicrobial effects of UMFix, an alcohol based tissue fixative, on various microorganisms. The UMFix solution was compared with 10% neutral buffered formalin.

  4. Antimicrobial activity of poly(acrylic acid) block copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Gratzl, Günther, E-mail: guenther.gratzl@jku.at [Johannes Kepler University Linz, Institute for Chemical Technology of Organic Materials, Altenberger Str. 69, 4040 Linz (Austria); Paulik, Christian [Johannes Kepler University Linz, Institute for Chemical Technology of Organic Materials, Altenberger Str. 69, 4040 Linz (Austria); Hild, Sabine [Johannes Kepler University Linz, Institute of Polymer Science, Altenberger Str. 69, 4040 Linz (Austria); Guggenbichler, Josef P.; Lackner, Maximilian [AMiSTec GmbH and Co. KG, Leitweg 13, 6345 Kössen, Tirol (Austria)

    2014-05-01

    The increasing number of antibiotic-resistant bacterial strains has developed into a major health problem. In particular, biofilms are the main reason for hospital-acquired infections and diseases. Once formed, biofilms are difficult to remove as they have specific defense mechanisms against antimicrobial agents. Antimicrobial surfaces must therefore kill or repel bacteria before they can settle to form a biofilm. In this study, we describe that poly(acrylic acid) (PAA) containing diblock copolymers can kill bacteria and prevent from biofilm formation. The PAA diblock copolymers with poly(styrene) and poly(methyl methacrylate) were synthesized via anionic polymerization of tert-butyl acrylate with styrene or methyl methacrylate and subsequent acid-catalyzed hydrolysis of the tert-butyl ester. The copolymers were characterized via nuclear magnetic resonance spectroscopy (NMR), size-exclusion chromatography (SEC), Fourier transform infrared spectroscopy (FTIR), elemental analysis, and acid–base titrations. Copolymer films with a variety of acrylic acid contents were produced by solvent casting, characterized by atomic force microscopy (AFM) and tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antimicrobial activity of the acidic diblock copolymers increased with increasing acrylic acid content, independent of the copolymer-partner, the chain length and the nanostructure. - Highlights: • Acrylic acid diblock copolymers are antimicrobially active. • The antimicrobial activity depends on the acrylic acid content in the copolymer. • No salts, metals or other antimicrobial agents are needed.

  5. High concentration bile combined with infection induces pro-inflammatory reaction through activation of the inflammasome in monocytes%高浓度胆汁合并感染在炎症小体平台触发前炎症反应

    Institute of Scientific and Technical Information of China (English)

    陈振勇; 涂志刚; 冯贤松; 王延刚; 杨鹏; 蒋春舫

    2012-01-01

    Objective To investigate the signal pathway of high concentration bile triggering monocyte proinflammatory response.Methods The peripheral blood monouclear cells (PBMCs) of rats were isolated and cultured in vitro.The concentration of 5% bile in rats was prepared.The PBMCs were cocultured with 5% bile,endotoxin (LPS),adenosine-triphosphate (ATP),or high K+ culture fluid.The cytotoxicity was detected by lactate dehydrogenase (LDH) after 1,6,12,and 24 h.The contents of interleukin (IL)-1β were determined by using enzyme linked immunosorbent assay (ELIAS),and the expression of Caspase-1 and NALP3 was detected by using Western blotting and analyzed quantitatively.Results 5% bile only was failed to induce expression of interleukin (IL)-1β,Caspase-1 or NALP3.But the levels of IL-1β were increased to (769.8 ± 29.4) and (788.6 ± 32.4) ng/L after pretreatment with LPS or ATP,which were significantly higher than single LPS group [(88.1 ±6.7) ng/L,P <0.01].The levels of IL-1β reached the peak [(871.1 ± 69.7) ng/L] at 6th h after pretreatment with LPS.There was no correlation between LDH and IL-1β.Western blotting analysis demonstrated that the Caspase-1 protein generated a band about 1.0 × 104 and a broad band about 1.2 × 105 of NALP3 in LPS + bile group.The quantitative analysis showed that the expression of Caspase-1 and NALP3 was higher obviously in LPS + bile group than that in single LPS group.Concentration of IL-1β was decreased in LPS + bile group after culture with high K+ substratum for 6 h.Conclusion The high concentration of bile in the blood circulation combined with bacterial infection induces proinflammatory responses via activation of the NLRP3 inflammasome.The potassium efflux is required for the procedure.%目的 观察高浓度胆汁成分触发前炎症反应的途径.方法 分离培养大鼠外周血单核细胞,分别与5%胆汁、内毒素(LPS)、三磷酸腺苷(ATP)、高K+培养液接触,采用乳酸脱氢酶(LDH)检测细胞毒

  6. Activity of Antimicrobial Silver Polystyrene Nanocomposites

    Directory of Open Access Journals (Sweden)

    M. Palomba

    2012-01-01

    Full Text Available A simple technique based on doping polymers with in situ generated silver nanoparticles (Ag/PS films has been developed. In particular, an antiseptic material has been prepared by dissolving silver 1,5-cyclooctadiene-hexafluoroacetylacetonate in amorphous polystyrene, and the obtained solid solution has been heated for ca. 10 s at a convenient temperature (180°C. Under such conditions the metal precursor decomposes producing silver atoms that diffuse into the polymer and clusterize. The antimicrobial characteristics of the resulting polystyrene-based material have been accurately evaluated toward Escherichia coli (E. coli comparing the cytotoxicity effect of 10 wt.% and 30 wt.% (drastic and mild annealing silver-doped polystyrene to the corresponding pure micrometric silver powder. Two different bacterial viability assays were performed in order to demonstrate the cytotoxic effect of Ag/PS films on cultured E. coli: (1 turbidimetric determination of optical density; (2 BacLight fluorescence-based test. Both methods have shown that silver-doped polystyrene (30 wt.% provides higher antibacterial activity than pure Ag powder, under similar concentration and incubation conditions.

  7. Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

    Science.gov (United States)

    Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

    2016-01-01

    Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

  8. Identification of (poly)phenol treatments that modulate the release of pro-inflammatory cytokines by human lymphocytes.

    Science.gov (United States)

    Ford, Christopher T; Richardson, Siân; McArdle, Francis; Lotito, Silvina B; Crozier, Alan; McArdle, Anne; Jackson, Malcolm J

    2016-05-28

    Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation. PMID:26984113

  9. Expression of pathogen recognition receptors and pro-inflammatory cytokine transcripts in clinical and sub-clinical endometritis cows.

    Science.gov (United States)

    Loyi, Tumnyak; Kumar, Harendra; Nandi, Sukdeb; Patra, Manas Kumar

    2015-01-01

    The present study was carried out to examine the expression profile of pathogen recognition receptors (CD14 and toll-like receptor 4) and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNFα) in endometrial tissue of cows with endometritis at different stages of estrous cycle. Genital tracts were collected from 60 cows at slaughter from the killing village. The genitalia were examined for clinical endometritis (CE) and subclinical endometritis (SCE) through physical examination, white side test of cervico-vaginal mucus, endometrial cytology and histopathology. The stage of estrous cycle for each genitalia was determined by visual examination of both the ovaries and classified as either follicular (F) or luteal (L). Depending on the degree of inflammation and stage of estrous cycle, the genitalia were categorized in four groups i.e., FCE, FSCE, LCE, and LSCE with six genitalia in each group. Furthermore, 12 healthy genitalia comprise of six each of follicular (FN) and luteal (LN) were included as control. Endometrial tissue scrapings were collected ex vivo from all the genitalia. Total RNA was extracted and cDNA was transcribed for each sample and relative quantification of mRNA of target genes was done by real-time PCR. The results revealed a significant up-regulation of CD14 (11 fold) and IL-8 (13 fold) in follicular stage and IL-6 (8 fold) and TNFα (29 fold) in luteal stages in SCE cows. However, the majority of pro-inflammatory cytokine and pathogen recognition receptors expressed at significant higher level in both follicular and luteal stages in cows with CE. Thus, it is concluded that the endometrial transcripts of pathogen recognition receptors and pro-inflammatory cytokines expressed differentially in cows with endometritis, whereas the fold change is dependent on the severity of inflammation and the stage of cyclicity. Therefore, endometrial transcript profile with a defined threshold level could be used as a possible diagnostic marker in cows with

  10. REACTION AROILMETHYLENTRIPHENILPHOSPHRILIDES WITH ARILDIASONIY BORPHTORIDES AND ANTIMICROBIAL ACTIVITY PHOSPHONIYHIDROSONES

    Directory of Open Access Journals (Sweden)

    Malanchuk SG

    2013-06-01

    Full Text Available The reactions of electrophilic accession borftoryds aryldizoniy by P-C connection aroyilmetylentryphenylfosforilids were studied. Found that the reaction formed borftoryds hidrazonofosfoniy salts. Studied the chemical and physical properties and antimicrobial activity of synthesized compounds.

  11. ANTIMICROBIAL ACTIVITY OF MEDICINAL PLANTS AGAINST DIFFERENT STRAINS OF BACTERIA

    OpenAIRE

    Alexander Vatľák; Adriana Kolesárová; Nenad Vukovič; Katarína Rovná; Jana Petrová; Viktória Vimmerová; Lukáš Hleba; Martin Mellen; Miroslava Kačániová

    2014-01-01

    In this study, methanolic extracts of Tilia cordata Mill. and Aesculus hippocastanum which had been described in herbal books, were screened for their antimicrobial activity against gramnegative and grampositive bacteria. The following strains of bacteria for antimicrobial activity were used gramnegative bacteria: Escherichia coli CCM 3988, Listeria ivanovii CCM 5884, Listeria innocua CCM 4030, Pseudomonas aeruginosa CCM 1960, Serratia rubidaea CCM 4684 and grampositive bacteria: Brochothrix ...

  12. Antimicrobial and antipathogenic activity of Fallopia japonica leaves alcoholic extract

    OpenAIRE

    Ioana-Cristina Marinaş; Elisabeta-Irina Geană; Eliza Oprea; Carmen Chifiriuc; Veronica Lazăr

    2014-01-01

    The aim of the study consists in the investigation of the antimicrobial and antiphatogenic activity of ethanol extracts obtain from F. japonica leaves. Total phenolic content was determined by Folin-Ciocalteu method, while their phenolic composition was specified by HPLC. In vitro antimicrobial activity of various concentrations ranging from 6.25 to 200 μL/mL of alcoholic (ethanol 70%) extract of F. japonica were analyzed on different clinical and reference bacterial strains (Staphylococcus a...

  13. Antimicrobial, antibiofilm and cytotoxic activities of Hakea sericea Schrader extracts

    OpenAIRE

    Ângelo Luís; Luiza Breitenfeld; Susana Ferreira; Ana Paula Duarte; Fernanda Domingues

    2014-01-01

    Background: Hakea sericea Schrader is an invasive shrub in Portuguese forests. Objective: The goal of this work was to evaluate the antimicrobial activity of H. sericea extracts against several strains of microorganisms, including the ability to inhibit the formation of biofilms. Additionally the cytotoxic properties of these extracts, against human cells, were assessed. Materials and Methods: The antimicrobial activity of the methanolic extracts of H. sericea was assessed by disk diffusion a...

  14. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    International Nuclear Information System (INIS)

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  15. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    Energy Technology Data Exchange (ETDEWEB)

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio, E-mail: yyoneda@p.kanazawa-u.ac.jp

    2014-10-03

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  16. The antimicrobial activity of the Cnicus benedictus L. extracts

    Directory of Open Access Journals (Sweden)

    Annamaria PALLAG

    2009-05-01

    Full Text Available Our goal was to test the antimicrobial effect of the aqueous solutions obtained from the soft extract of Cnicus benedictus L. (Asteraceae family flowers. The test was performed on Mueller - Hinton and blood-agar culture medium, on 8 standardized bacterial strains and microbiological strains obtained from infected secretions, using the diffusimetric method.The antimicrobial action of the plant extracts was confirmed by all bacterial tested strains, which presented inhibition zones, of approximately same values, at solutions with different concentrations. The values we obtained reveal significant differences of the intensity of the antimicrobial activity of the mature and immature flowers extract.

  17. Synergistic effect of simvastatin and ezetimibe on lipid and pro-inflammatory profiles in pre-diabetic subjects

    Directory of Open Access Journals (Sweden)

    Kater Ana-Lucia A

    2010-06-01

    Full Text Available Abstract Background Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial. Objective This open-label trial evaluated whether the combination of simvastatin and ezetimibe also results in a synergistic effect that reduces the pro-inflammatory status of pre-diabetic subjects. Methods Fifty pre-diabetic subjects were randomly assigned to one of 2 groups, one receiving ezetimibe (10 mg/day, the other, simvastatin (20 mg/d for 12 weeks, followed by an additional 12-week period of combined therapy. Blood samples were collected at baseline, 12 and 24 weeks. RESULTS: Total cholesterol, LDL-cholesterol and apolipoprotein B levels decreased in all the periods analyzed (p Conclusion Expected synergistic lowering effects of a simvastatin and ezetimibe combination on LDL-cholesterol, apolipoprotein B and triglycerides levels were confirmed in subjects with early disturbances of glucose metabolism. We suggest an additive effect of this combination also on inflammatory status based on the reduction of C-reactive protein. Attenuation of pro-inflammatory conditions may be relevant in reducing cardiometabolic risk. Title/ID of trial registration Effect of simvastatin and ezetimibe on lipid and inflammation/NCT01103648.

  18. Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83.

    Directory of Open Access Journals (Sweden)

    Vivekanandhan Aravindhan

    Full Text Available Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416 as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%] compared to pre-diabetic subjects [9.1%] (p = 0.0095 and non-diabetic subjects [10.4%] (p = 0.0463. A significant decrease in filarial antigen load (p = 0.04 was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines-IL-6 and GM-CSF-were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines-IL-10, IL-13 and TGF-beta-between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF.

  19. An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines.

    Science.gov (United States)

    Utrera-Barillas, Dolores; Velazquez, Juan R; Enciso, Antonio; Cruz, Samira Muñoz; Rico, Guadalupe; Curiel-Quesada, Everardo; Teran, Luis M; Kretschmer, Roberto R

    2003-10-01

    Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given. Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1alpha, MIP-1beta, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1alpha, MIP-1beta, and I-309, and that of the CCR1 receptor--all involved in monocyte chemotaxis--was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also--and perhaps foremost--through a conglomerate down-regulation of endogenous pro-inflammatory chemokines.

  20. Development of elastin-like recombinamer films with antimicrobial activity

    DEFF Research Database (Denmark)

    Costa, André; Machado, Raul; Ribeiro, Artur;

    2015-01-01

    In the present work we explored the ABP-CM4 peptide properties from Bombyx mori for the creation of biopolymers with broad antimicrobial activity. An antimicrobial recombinant protein-based polymer (rPBP) was designed by cloning the DNA sequence coding for ABP-CM4 in frame with the N-terminus of ......In the present work we explored the ABP-CM4 peptide properties from Bombyx mori for the creation of biopolymers with broad antimicrobial activity. An antimicrobial recombinant protein-based polymer (rPBP) was designed by cloning the DNA sequence coding for ABP-CM4 in frame with the N......-terminus of the elastin-like recombinamer consisting of 200 repetitions of the pentamer VPAVG, here named A200. The new rPBP, named CM4-A200, was purified via a simplified nonchromatographic method, making use of the thermoresponsive behavior of the A200 polymer. ABP-CM4 peptide was also purified through...... the incorporation of a formic acid cleavage site between the peptide and the A200 sequence. In soluble state the antimicrobial activity of both CM4-A200 polymer and ABP-CM4 peptide was poorly effective. However, when the CM4-A200 polymer was processed into free-standing films high antimicrobial activity against...

  1. Comparative Evaluation of the Antimicrobial Activity of Different Antimicrobial Peptides against a Range of Pathogenic Bacteria.

    Directory of Open Access Journals (Sweden)

    Anna Ebbensgaard

    Full Text Available The rapid emergence of resistance to classical antibiotics has increased the interest in novel antimicrobial compounds. Antimicrobial peptides (AMPs represent an attractive alternative to classical antibiotics and a number of different studies have reported antimicrobial activity data of various AMPs, but there is only limited comparative data available. The mode of action for many AMPs is largely unknown even though several models have suggested that the lipopolysaccharides (LPS play a crucial role in the attraction and attachment of the AMP to the bacterial membrane in Gram-negative bacteria. We compared the potency of Cap18, Cap11, Cap11-1-18m2, Cecropin P1, Cecropin B, Bac2A, Bac2A-NH2, Sub5-NH2, Indolicidin, Melittin, Myxinidin, Myxinidin-NH2, Pyrrhocoricin, Apidaecin and Metalnikowin I towards Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Aeromonas salmonicida, Listeria monocytogenes, Campylobacter jejuni, Flavobacterium psychrophilum, Salmonella typhimurium and Yersinia ruckeri by minimal inhibitory concentration (MIC determinations. Additional characteristics such as cytotoxicity, thermo and protease stability were measured and compared among the different peptides. Further, the antimicrobial activity of a selection of cationic AMPs was investigated in various E. coli LPS mutants.Of all the tested AMPs, Cap18 showed the most efficient antimicrobial activity, in particular against Gram-negative bacteria. In addition, Cap18 is highly thermostable and showed no cytotoxic effect in a hemolytic assay, measured at the concentration used. However, Cap18 is, as most of the tested AMPs, sensitive to proteolytic digestion in vitro. Thus, Cap18 is an excellent candidate for further development into practical use; however, modifications that should reduce the protease sensitivity would be needed. In addition, our findings from analyzing LPS mutant strains suggest that the core oligosaccharide of the LPS

  2. Nanoliposomes containing Eucalyptus citriodora as antibiotic with specific antimicrobial activity.

    Science.gov (United States)

    Lin, Lin; Cui, Haiying; Zhou, Hui; Zhang, Xuejing; Bortolini, Christian; Chen, Menglin; Liu, Lei; Dong, Mingdong

    2015-02-14

    Bacterial infections are a serious issue for public health and represent one of the major challenges of modern medicine. In this work, a selective antimicrobial strategy based on triggering of pore-forming toxin, which is secreted by infective bacteria, was designed to fight Staphylococcus aureus. The antimicrobial activity is realized by employing Eucalyptus citriodora oil as antibiotic which in this study is encapsulated in nanoliposomes. PMID:25573466

  3. Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Stephanie Siegl

    Full Text Available INTRODUCTION: The mechanisms of ventilator-induced lung injury (VILI, including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV on pro-inflammatory signaling events in two widely used mouse strains (C57BL/6, BALB/c and to further define the role of p38 in VILI. METHODS: Lungs were perfused and ventilated for 30 min under control conditions before they were randomized to low (8 cm H(2O or high (25 cm H(2O pressure ventilation (HPV for 210 min, with the left lung being removed after 180 min. In the left lung we measured the phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg. RESULTS: Lung mechanics and kinase activation were similar in both mouse strains. HPV increased all genes (except Tnf in BALB/c and all mediators in both strains. The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c mice. Backward regression of the kinase data at t = 180 min with the gene and protein expression data at t = 240 min suggested that p38 controls HPV-induced gene expression, but not protein production. This hypothesis was confirmed in experiments with the p38-kinase inhibitor SB203580. CONCLUSIONS: The one-lung method is useful for mechanistic studies in the lungs. While C57BL/6 show diminished pro-inflammatory responses during HPV, lung mechanics and mechanotransduction processes appear to be similar in both mouse strains. Finally, the one-lung method allowed us to link p38 to gene expression during VILI.

  4. Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats

    Directory of Open Access Journals (Sweden)

    Roussel Anne M

    2007-01-01

    Full Text Available Abstract Background Tristetraprolin (TTP/ZFP36 family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. We hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. Methods Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3, pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2, and Elavl1/Hua/Hur and Vegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. Results Ttp and Zfp36l1 mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle. Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid extract/kg diet increased Ttp mRNA levels by 50–140% but Tnf mRNA levels decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in the muscle. Tea (2 g solid extract/kg diet increased Elavl1/Hua/Hur mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. Conclusion These results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases.

  5. CPU86017-RS attenuated hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    Guo-lin ZHANG; Feng YU; De-zai DAI; Yu-si CHENG; Can ZHANG; Yin DAI

    2012-01-01

    Aim:Downregulation of androgen biosynthesis genes StAR (steroidogenic acute regulatory)and 3β-HSD (3β-hydroxysteroid dehydrogenase)contributes to low testosterone levels in hypoxic mice and is possibly related to increased expression of pro-inflammatory cytokines in the testis.The aim of this study is to investigate the effects of CPU86017-RS that block Ca2+ influx on hypoxia-induced testis insult in mice.Methods:Male ICR mice were divided into 5 groups:control group,hypoxia group,hypoxia group treated with nifedipine (10 mg/kg),hypoxia groups treated with CPU86017-RS (60 or 80 mg/kg).Hypoxia was induced by placing the mice in a chamber under 10%+0.5% 02 for 28 d (8 h per day).The mice were orally administered with drug in the last 14 d.At the end of experiment the testes of the mice were harvested.The mRNA and protein levels of StAR,3β-HSD,connexin 43 (Cx43),matrix metalloprotease 9 (MMP9),endothelin receptor A (ETAR)and leptin receptor (OBRb)were analyzed using RT-PCR and Western blotting,respectively.The malondialdehyde (MDA),lactate dehydrogenase (LDH),succinate dehydrogenase (SDH)and acid phosphatase (ACP)levels were measured using biochemical kits.Serum testosterone concentration was measured with radioimmunoassay.Results:Hypoxia significantly increased the MDA level,and decreased the LDH,ACP and SDH activities in testes.Meanwhile,hypoxia induced significant downregulation of StAR and 3β-HSD in testes responsible for reduced testosterone biosynthesis.It decreased the expression of Cx43,and increased the expression of MMP9,ETAR and OBRb,leading to abnormal testis function and structure.These changes were effectively diminished by CPU86017-RS (80 mg/kg)or nifedipine (10 mg/kg).Conclusion:Low plasma testosterone level caused by hypoxia was due to downregulation of StAR and 3β-HSD genes,in association with an increased expression of pro-inflammatory cytokines.These changes can be alleviated by CPU86017-RS or nifedipine.

  6. Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, PPARgamma agonists, differentially regulate cigarette smoke-mediated pro-inflammatory cytokine release in monocytes/macrophages.

    Science.gov (United States)

    Caito, Samuel; Yang, Se-Ran; Kode, Aruna; Edirisinghe, Indika; Rajendrasozhan, Saravanan; Phipps, Richard P; Rahman, Irfan

    2008-02-01

    Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) ligands have the potential for use as anti-inflammatory agents in chronic airway diseases. We hypothesized that cigarette smoke (CS)-mediated pro-inflammatory cytokine release would be downregulated in the monocyte-macrophage cell line (MonoMac6) by synthetic and natural PPARgamma ligands. Surprisingly, treatment of MonoMac6 cells with the natural PPARgamma ligand 15-deoxy-Delta12,14-prostaglandin J2 led to increased cytokine (IL-8) release in response to either TNF-alpha or CS extract (CSE). However, exposure to rosiglitazone, a synthetic agonist, led to decreased TNF-alpha, but not CSE, mediated cytokine release. Cytokine release correlated with nuclear PPARgamma localization; CSE reduced the amount of activated PPARgamma located in the nucleus and formed aldehyde adducts as PPARgamma protein carbonyls. Furthermore, it was shown that PPARgamma interacts with the RelA/p65 subunit of NF-kappaB under TNF-alpha exposure conditions, but this interaction was disrupted by CS exposure, suggesting that CS blocks this important anti-inflammatory pathway involving PPARgamma. Thus, these new data show that activation of PPARgamma with natural or synthetic ligands have differential inhibitory effects on CS-mediated pro-inflammatory mediator release. These data have implications in designing therapies for treatment of COPD and pulmonary fibrosis. PMID:17970647

  7. Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages.

    Science.gov (United States)

    Pucca, Manuela B; Peigneur, Steve; Cologna, Camila T; Cerni, Felipe A; Zoccal, Karina F; Bordon, Karla de C F; Faccioli, Lucia H; Tytgat, Jan; Arantes, Eliane C

    2015-08-01

    Tityus serrulatus (Ts) venom is composed of mainly neurotoxins specific for voltage-gated K(+) and Na(+) channels, which are expressed in many cells such as macrophages. Macrophages are the first line of defense invasion and they participate in the inflammatory response of Ts envenoming. However, little is known about the effect of Ts toxins on macrophage activation. This study investigated the effect of Ts5 toxin on different sodium channels as well as its role on the macrophage immunomodulation. The electrophysiological assays showed that Ts5 inhibits the rapid inactivation of the mammalian sodium channels Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6 and Nav1.7. Interestingly, Ts5 also inhibits the inactivation of the insect Drosophila melanogaster sodium channel (DmNav1), and it is therefore classified as the first Ts α-like toxin. The immunological experiments on macrophages reveal that Ts5 is a pro-inflammatory toxin inducing the cytokine production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. On the basis of recent literature, our study also stresses a possible mechanism responsible for venom-associated molecular patterns (VAMPs) internalization and macrophage activation and moreover we suggest two main pathways of VAMPs signaling: direct and indirect. This work provides useful insights for a better understanding of the involvement of VAMPs in macrophage modulation. PMID:25906692

  8. Wear particle-mediated expressions of pro-inflammatory cytokines,NF-κB and RANK were impacted by lanthanum chloride in RAW264.7 cells

    Institute of Scientific and Technical Information of China (English)

    DAI Min; JIANG Chuan; LIU Xiang; LI Zhe; CHENG Xigao; ZOU Yang; NIE Tao

    2013-01-01

    To explore the impact of different concentrations of lanthanum chloride (LaCl3) on critical components of wear particle-mediated signaling pathways in inflammation and osteoclastogenesis,RAW264.7 cells were naturally divided into eight groups and analyzed by CCK-8 assay,flow cytometry,ELISA,RT-PCR and western blot after treatments.The results showed that three concentrations of LaCl3 had no influence on viability of RAW264.7 cells and down-regulated receptor activator of nuclear factor κB (RANK) instead of macrophage colony-stimulating factor receptor (M-CSFR).Additionally,2.5 and 10 μmol/L LaCl3 could signifi-cantly inhibit gene and protein levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-lβ,i.e.,TNF-α and IL-1β) and NF-κB/p65,but 100 μrnol/L LaCl3 did not exert an obvious inflammation-inhibiting effect,and even induced inflammation.In conclusion,these findings demonstrated that LaC13 was able to suppress wear particle-induced inflammation and activation of NF-κB in a certain range of concentrations in vitro and mainly decrease the expression of RANK,but not M-CSFR,all of which were generally recognized to play a pivotal role in osteoclastogenesis.

  9. The long polar fimbriae of STEC O157:H7 induce expression of pro-inflammatory markers by intestinal epithelial cells.

    Science.gov (United States)

    Farfan, Mauricio J; Cantero, Lidia; Vergara, Alejandra; Vidal, Roberto; Torres, Alfredo G

    2013-03-15

    Infection with Shiga toxin-producing Escherichia coli (STEC) O157:H7 is characterized by acute inflammation of the colonic mucosa. STEC O157:H7 contains two non-identical loci encoding long polar fimbriae (Lpf), which play a role in the STEC colonization of the intestinal epithelial cells. However, no information is available regarding the involvement of Lpf in the STEC-induced host inflammatory response. Hence, in this study we assess the role of Lpf as an inducer of inflammation on intestinal epithelial cells. Secretion of pro-inflammatory cytokines in response to STEC wild type and lpf isogenic mutants was evaluated on intestinal T84 cells. Of the 27 cytokines assayed, IL-6, IL-8, IL-15, FGF, GM-CSF and IP-10 were significantly reduced, when compared to the wild-type strain, in the lpfA1 lpfA2 double mutant. Further, the host intracellular signaling pathways activated in response to Lpf were determined by using an array containing genes representative of 18 different signal transduction pathways. The analysis indicated that the NF-κB pathway is activated in response to Lpf-expressing STEC. Therefore, our study supports the role of Lpf as a STEC factor mediating intestinal inflammation.

  10. Real time macrophage migration analysis and associated pro-inflammatory cytokine release on transparent carbon nanotube/polymer composite nano-film

    Science.gov (United States)

    Khang, Dongwoo

    2015-08-01

    Surface chemistry and nanoscale surface morphology are both influential factors for cell adhesion, growth, and differentiation. In particular, cell migration is one of the major markers of initial immune response activation to implanted biomaterials. Despite their indication, it has been difficult to directly examine macrophages on nanoscale materials, because most nanomaterials possess greater thicknesses than nanoscale. This study developed transparent films comprising a carbon nanotube and polymer composite with controlled surface stiffness and nanoscale roughness. As nanoscale surface topography can incite immune cell activation, analysis of the real-time cell migration (including velocity) of macrophages due to changes in nanoscale surface topography of a biopolymer can support the direct relationship between initial macrophage dynamics and corresponding pro-inflammatory responses. Through real-time analysis, we have identified that surface chemistry and surface nanoscale topography are both independent factors mediating macrophage interactions, and, thus, immune cell behavior can be further controlled by the systematic variation of nanoscale surface topography for a given surface chemistry. Considering that the initial immune response can determine the fate and lifetime of implanted biomaterials, this study presents the direct relationship between initial macrophage dynamics and subsequent inflammatory cytokine release on transparent carbon nanotube polymer composites.

  11. Phytochemical characterization and antimicrobial activity of Curcuma xanthorrhiza Roxb.

    Institute of Scientific and Technical Information of China (English)

    Mary Helen PA; Susheela Gomathy K; Jayasree S; Nizzy AM; Rajagopal B; Jeeva S

    2012-01-01

    Objective: To study the antimicrobial activity and phytochemical characterization of essential oil isolated from the rhizome of Curcuma xanthorrhiza against pathogenic bacteria and fungi.Methods:Fresh rhizomes of Curcuma xanthorrhiza were subjected to hydro distillation process to obtain essential oil and characterized by Gas Chromatography- Mass Spectroscopy (GC-MS). The essential oil was evaluated for antibacterial and antifungal activity against thirteen pathogenic bacteria and six fungi by the disc diffusion method. Results: GC – MS analysis of the essential oil extracted from the rhizome of Curcuma xanthorrhiza contained the derivatives of xanthorihizol, camphene and curcumene, monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene, hydrocarbons and other minor compounds. The antimicrobial activity of the oil showed significant inhibitory activity against the human pathogenic bacteria, no activity was observed against the fungi Aspergillus niger and Fusarium oxysporum. Conclusions: The findings of the present study indicate that the rhizome extract of Curcuma xanthorrhiza possess secondary metabolites and potential to develop antimicrobial drugs.

  12. Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Juan David Guzman

    2014-11-01

    Full Text Available Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  13. Enhancement of antimicrobial activity of chitosan by irradiation

    International Nuclear Information System (INIS)

    Antimicrobial activity of irradiated chitosan was studied against Escherichia coli B/r. Irradiation of chitosan at 100 kGy under dry conditions was effective in increasing the activity, and inhibited the growth of E. coli completely. The molecular weight of chitosan significantly decreased with the increase in irradiation dose, whereas the relative surface charge of chitosan was decreased only 3% by 100 kGy irradiation. Antimicrobial activity assay of chitosan fractionated according to molecular weight showed that 1 x 105-3 x 105 fraction was most effective in suppressing the growth of E coli. This fraction comprised only 8% of the 100 kGy irradiated chitosan. On the other hand, chitosan whose molecular weight was less than 1 x 105 had no activity. The results show that low dose irradiation, specifically 100 kGy, of chitosan gives enough degradation to increase its antimicrobial activity as a result of a change in molecular weight. (Author)

  14. Antimicrobial and Antioxidant Activity of Fruit Pulp of Livistonia Chinensis

    OpenAIRE

    Tanu P; Thakur K; Kaur G

    2013-01-01

    The present study reveals the in-vitro antimicrobial activity and antioxidant activity of ethanolic extractof fruit pulp of plant of Livistonia chinensis has been evaluated using disc diffusion method againstbacterial strains of Bacillus subtilis, Staphylococcus aureus, Shigella dysenteriae, Salmonella enteritidisand fungal strain of Candida albicans using specific standard Ciprofloxacin and Fluconazolerespectively and DPPH method for antioxidant activity.

  15. Effects of deer bone extract on the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced osteoarthritic rats.

    Science.gov (United States)

    Lee, Hyunji; Choi, Hyeon-Son; Park, Yooheon; Ahn, Chang Won; Jung, Sung Ug; Park, Soo Hyun; Suh, Hyung Joo

    2014-01-01

    Deer bone extract has the potential to relieve the discomfort or the articular cartilaginous damage associated with osteoarthritic (OA) and may be useful as a natural supplement for OA treatment without serious side effects. We analyzed the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced OA rats. Increases in the levels of serum pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly inhibited by the administration of deer bone extract (pCOL2) and tissue inhibitors of metalloproteinases (TIMPs) mRNAs in the cartilage were significantly inhibited by deer bone extract treatment (pCOL2 and TIMP mRNAs and the down-regulation of MMP mRNAs by suppressing the expression of pro-inflammatory cytokine mRNAs. PMID:25273135

  16. Study Antimicrobial Activity of Lemon (Citrus lemon L. Peel Extract

    Directory of Open Access Journals (Sweden)

    Maruti J. Dhanavade

    2011-08-01

    Full Text Available The main objective of the study is extraction, identification of antimicrobial compounds and demonstration of antimicrobial activity of lemon (Citrus lemon L. peel against bacteria. As microorganism are becoming resistant to present day antibiotics, our study focuses on antimicrobial activity and future prophylactic potential of the lemon peel. Biologically active compounds present in the medicinal plants have always been of great interest to scientists. The peel of citrus fruits is a rich source of flavanones and many polymethoxylated flavones, which are very rare in other plants. These compounds, not only play an important physiological and ecological role, but are also of commercial interest because of their multitude of applications in the food and pharmaceutical industries. The citrus peel oils show strong antimicrobial activity. The antimicrobial activity has been checked in terms of MIC by using different solvents against microorganisms like Pseudomonas aeruginosa NCIM 2036 for which MIC was 1:20 in presence of methanol, for Salmonella typhimurium NCIM 5021 the observed MIC was 1:20 in presence of acetone. In case of Micrococcus aureus NCIM 5021 the observed MIC was 1:20 when ethanol was used as solvent. The compounds like coumarin and tetrazene were identified by GC/MS of lemon peel extract.

  17. Antimicrobial peptides: a review of how peptide structure impacts antimicrobial activity

    Science.gov (United States)

    Soares, Jason W.; Mello, Charlene M.

    2004-03-01

    Antimicrobial peptides (AMPs) have been discovered in insects, mammals, reptiles, and plants to protect against microbial infection. Many of these peptides have been isolated and studied exhaustively to decipher the molecular mechanisms that impart protection against infectious bacteria, fungi, and viruses. Unfortunately, the molecular mechanisms are still being debated within the scientific community but valuable clues have been obtained through structure/function relationship studies1. Biophysical studies have revealed that cecropins, isolated from insects and pigs, exhibit random structure in solution but undergo a conformational change to an amphipathic α-helix upon interaction with a membrane surface2. The lack of secondary structure in solution results in an extremely durable peptide able to survive exposure to high temperatures, organic solvents and incorporation into fibers and films without compromising antibacterial activity. Studies to better understand the antimicrobial action of cecropins and other AMPs have provided insight into the importance of peptide sequence and structure in antimicrobial activities. Therefore, enhancing our knowledge of how peptide structure imparts function may result in customized peptide sequences tailored for specific applications such as targeted cell delivery systems, novel antibiotics and food preservation additives. This review will summarize the current state of knowledge with respect to cell binding and antimicrobial activity of AMPs focusing primarily upon cecropins.

  18. The Medicinal Plant of Mimusops Elengi (Sapodaceae in Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Kannadhasan M.

    2016-07-01

    Full Text Available The selected study area for this study is Pachaimalai Hills, situated in Eastern ghats of Tamil Nadu. This study was focussed on the antimicrobial activity of Mimosopselengi, one of the medicinal plant belongs to the family sapotaceae. It is a tropically distributed the highly medicinal plant. Antimicrobial activities and extracts of petroleum ether, Ethyl acetate and methanol were also found to be better with respect to inhibitory function against the two fungal species, Fusarium oxysporum and Aspergillus flavus. The study scientifically validates the use of plant in traditional and ethno medicine. Three solvents such as Petroleum ether, Ethyl acetate and Ethanol were used to take plant extract. These extracts were studied for antimicrobial activity against two gram positive bacterial strains such as Bacillus substilis andBacillus thuriengensis and two gram negative bacterial strains such as Klebsiella pneumonia and Escherichia coli. This study also extended to find antifungal activity against four fungal strains.

  19. Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.

    Directory of Open Access Journals (Sweden)

    Alessandro Rolfo

    Full Text Available UNLABELLED: The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs derived from normal and preeclamptic (PE chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF, Vascular Endothelial Growth Factor (VEGF, soluble FMS-like tyrosine kinase-1 (sFlt-1 and free β-human Chorionic Gonadotropin (βhCG by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12 and physiological control term (n = 12 placentae. Control and PE-PDMSCs's cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM was collected. Physiological villous explants (n = 48 were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs

  20. Lignan Derivatives from Krameria lappacea Roots Inhibit Acute Inflammation in Vivo and Pro-inflammatory Mediators in Vitro

    OpenAIRE

    Baumgartner, Lisa; Sosa, Silvio; Atanasov, Atanas G.; Bodensieck, Antje; Fakhrudin, Nanang; Bauer, Julia; Favero, Giorgia Del; De Ponti, Cristina; Heiss, Elke H; Schwaiger, Stefan; Ladurner, Angela; Widowitz, Ute; Loggia, Roberto Della; Rollinger, Judith M.; Werz, Oliver

    2011-01-01

    The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1–11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID50 77 μg/cm2) as...

  1. ANTIMICROBIAL ACTIVITY OF THE FRUIT-SEEDS MADHUCA LONGIFOLIA (KOENIG

    Directory of Open Access Journals (Sweden)

    Chirantan S Chakma

    2011-09-01

    Full Text Available The investigation was carried out to study the antibacterial activity of the Madhuca longifolia(Koenig in gram positive and gram negative organism.. Antimicrobial activity of the acetone and aqueous extracts of M.longifolia were determined against various pathogenic bacteria. The extracts were tested against various bacteria like Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginos, .E.coli by disk diffusion method. Minimum Inhibitory Concentration (MIC values of both extracts were determined. It is concluded that acetone extract exhibited significant antimicrobial activity. The study lends scientific support for it’s use in folk medicine.

  2. Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model.

    Science.gov (United States)

    Hegazy, Hoda G; Ali, Elham H A; Elgoly, Amany H Mahmoud

    2015-02-01

    Butyl paraben is a preservative used in food, drugs and cosmetics. Neurotoxic effect was reported recently beside the potential estrogenic activity of parabens. There is controversy as to the potential harmful effects of butyl parabens, which are suspected to contribute to autism and learning disabilities. The purpose of this study was to examine the similarities between paraben intoxication signs in the rat brain and brain markers in an autistic like rat model. This study provides evidence of many parallels between the two, including (1) oxidative stress, (2) decreased reduced glutathione levels and elevated oxidised glutathione, (3) mitochondrial dysfunction, and (4) neuroinflammation and increased pro-inflammatory cytokine levels in the brain (tumour necrosis factor-alpha, interleukin-1-beta, and interleukin-6). (5) Increased protein oxidation reported by a significant increase in 3-nitrotyrosine (3-NT)/tyrosine ratio. (6) A marked disturbance was found in the production of energy carriers (AMP, ATP and AMP/ATP ratio) in comparison with the control. The evidence suggests that paraben may, to some extent, either cause or contribute to the brain physiopathology in ASDs or pathogens that produce the brain pathology observed in the diagnosed rat model of ASD.

  3. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes – A role for the transcription factor NFAT and phosphodiesterase 3B

    International Nuclear Information System (INIS)

    Highlights: ► GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. ► GIP-induced osteopontin expression is NFAT-dependent. ► Osteopontin expression is PDE3-dependent. ► Osteopontin expression is increased in PDE3B KO mice. -- Abstract: The incretin – glucose-dependent insulinotropic polypeptide (GIP) – and the pro-inflammatory cytokine osteopontin are known to have important roles in the regulation of adipose tissue functions. In this work we show that GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. The GIP-induced increase in osteopontin expression was inhibited by the NFAT (the transcription factor nuclear factor of activated T-cells) inhibitor A-285222. Also, the NFAT kinase glycogen synthase kinase (GSK) 3 was upregulated by GIP. To test whether cAMP might be involved in GIP-mediated effects on osteopontin a number of strategies were used. Thus, the β3-adrenergic receptor agonist CL316,243 stimulated osteopontin expression, an effects which was mimicked by OPC3911, a specific inhibitor of phosphodiesterase 3. Furthermore, treatment of phosphodiesterase 3B knock-out mice with CL316,243 resulted in a dramatic upregulation of osteopontin in adipose tissue which was not the case in wild-type mice. In summary, we delineate mechanisms by which GIP stimulates osteopontin in adipocytes. Given the established link between osteopontin and insulin resistance, our data suggest that GIP by stimulating osteopontin expression, also could promote insulin resistance in adipocytes.

  4. The frustrated host response to Legionella pneumophila is bypassed by MyD88-dependent translation of pro-inflammatory cytokines.

    Directory of Open Access Journals (Sweden)

    Seblewongel Asrat

    2014-07-01

    Full Text Available Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the host immune response in order to survive and replicate intracellularly. Legionella pneumophila, the causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its host cytosol through its type IV protein secretion machinery. At least 5 of the bacterial translocated effectors interfere with the function of host cell elongation factors, blocking translation and causing the induction of a unique host cell transcriptional profile. In addition, L. pneumophila also interferes with translation initiation, by preventing cap-dependent translation in host cells. We demonstrate here that protein translation inhibition by L. pneumophila leads to a frustrated host MAP kinase response, where genes involved in the pathway are transcribed but fail to be translated due to the bacterium-induced protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such as IL-1α and IL-1β, bypass this inhibition and get synthesized in the presence of Legionella effectors. We show that the selective synthesis of these genes requires MyD88 signaling and takes place in both infected cells that harbor bacteria and neighboring bystander cells. Our findings offer a perspective of how host cells are able to cope with pathogen-encoded activities that disrupt normal cellular process and initiate a successful inflammatory response.

  5. Antimicrobial activity of Gel-entrapped catechins toward oral microorganisms.

    Science.gov (United States)

    Tamura, Muneaki; Saito, Hideo; Kikuchi, Kuniyoshi; Ishigami, Tomohiko; Toyama, Yoshio; Takami, Masao; Ochiai, Kuniyasu

    2011-01-01

    The oral cavity contains almost half of the commensal bacterial population present in the human body. An increase in the number of these microorganisms may result in systemic diseases such as infective endocarditis and aspiration pneumonia as well as oral infections. It is essential to control the total numbers of these microorganisms in order to suppress disease onset. Thus, we examined the antimicrobial activity of a newly developed gel-entrapped catechin (GEC) preparation against oral microorganisms. The minimum inhibitory concentration (MIC) of GEC was determined based on the relationship between a modified agar diffusion method and a broth microdilution method. GEC inhibited the growth of the Actinomyces, periodontopathic bacteria and Candida strains tested, but did not inhibit the growth of the oral streptococci that are important in the normal oral flora. Commercially available moisture gels containing antimicrobial components showed antimicrobial activity against all of the tested strains. After a series of washes and after a 24-h incubation, GEC retained the antimicrobial activity of the catechins. Catalase prevented GEC-induced growth inhibition of Actinomyces naeslundii and Streptococcus mutans suggesting that hydrogen peroxide may be involved in the antimicrobial activity of catechins. These results suggest that GEC may be useful for controlling oral microorganism populations and reducing the accumulation of dental plaque, thereby helping to prevent periodontal disease and oral candidiasis. PMID:21532150

  6. Antimicrobial Activity of Metabolites of Various Strains of Lactobacillus acidophilus

    Directory of Open Access Journals (Sweden)

    Hassan Pyar Ali Hassan

    2011-01-01

    Full Text Available The antimicrobial activity of metabolites of eight strains of Lactobacillus acidophilus (FTDC 2804, FTDC 0785, FTDC 8592, FTDC 1295, FTDC 4793, FTDC 4462, FTDC 0582 and FTDC 2916 against  Staphylococcus aureus (gram positive and Escherichia coli (gram negative, was examined and compared using agar well diffusion method.  Lactobacillus acidophilus was cultivated in two different types of dairy growth medium namely, full cream milk and skim milk. The results showed that the metabolites of all the eight strains had significant antimicrobial effect based on zone of inhibition results when compared to control. There was a statistically significant difference in the zone of inhibition data for Staphylococcus aureus and Escherichia coli among the metabolites of the eight strains cultivated in the two different growth medium. Certain L. acidophilus strains were more effective against  Staphylococcus aureus, while other strains were more effective against  Escherichia coli. On the other hand, the growth medium had no significant influence on the antimicrobial effect of metabolites of seven strains except  L. acidophilus FTDC 4462 against Escherichia coli. As for  Staphylococcus aureus, the growth medium only affected the antimicrobial effect of metabolite of strain  L. acidophilus FTDC 1295, but did not affect the antimicrobial effect of metabolites of the other seven strains. It can be concluded that L. acidophilus cultivated in dairy products produced metabolites with antimicrobial property, which could provide beneficial medicinal values to human.

  7. Increased Pro-inflammatory Cytokines (TNF-a and IL-6 and Anti-inflammatory Compounds (sTNFRp55 and sTNFRp75 in Brazilian Patients during Exanthematic Dengue Fever

    Directory of Open Access Journals (Sweden)

    Luzia MO Pinto

    1999-05-01

    Full Text Available Pro-inflammatory cytokines, tumor necrosis factor (TNF-a, interleukin-6 (IL-6 and interleukin-1b (IL-1b as well as anti-inflammatory compounds, soluble TNF-Receptor p55 (sTNFRp55, sTNFRp75 and IL-1 receptor antagonist (sIL-1Ra, were investigated in 34 Brazilian cases of dengue fever (DF originated from a study of exanthematic virosis. The presence of pro-inflammatory cytokines was detected in sera from these patients by ELISA. TNF-a and IL-6 levels were significantly higher than control subjects in 32% and 52% patients, respectively. To our knowledge this was the first time a receptor antagonist and soluble receptors for cytokines were detected in sera obtained during exanthematic DF without hemorrhagic manifestations. Both sTNFRp55 and sTNFRp75 were consistently elevated in 42% and 84% patients, respectively. Most patients had IL-1b levels not different from those of normal subjects, except for one case. Only 16% patients had altered levels of IL-1Ra. Previous studies in dengue hemorrhagic fever patients demonstrated production of these soluble factors; here we observed that they are found in absence of hemorrhagic manifestations. The possible role of these anti-inflammatory compounds in immune cell activation and in regulating cytokine-mediated pathogenesis during dengue infection is discussed.

  8. Antimicrobial Activity of Chitosan-Carbon Nanotube Hydrogels

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2014-05-01

    Full Text Available In the present study, we have prepared chitosan-carbon nanotube (Chitosan-CNT hydrogels by the freeze-lyophilization method and examined their antimicrobial activity. Different concentrations of CNT were used in the preparation of Chitosan-CNT hydrogels. These differently concentrated CNT hydrogels were chemically characterized using Fourier Transform-Infrared Spectroscopy, Scanning Electron Microscopy and Optical microscopy. The porosity of the hydrogels were found to be >94%. Dispersion of chitosan was observed in the CNT matrix by normal photography and optical microscopy. The addition of CNT in the composite scaffold significantly reduced the water uptake ability. In order to evaluate antimicrobial activity, the serial dilution method was used towards Staphylococcus aureus, Escherichia coli and Candida tropicalis. The composite Chitosan-CNT hydrogel showed greater antimicrobial activity with increasing CNT concentration, suggesting that Chitosan-CNT hydrogel scaffold will be a promising biomaterial in biomedical applications.

  9. Synthesis and Antimicrobial Activity of Silver-Doped Hydroxyapatite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Carmen Steluta Ciobanu

    2013-01-01

    Full Text Available The synthesis of nanosized particles of Ag-doped hydroxyapatite with antibacterial properties is of great interest for the development of new biomedical applications. The aim of this study was the evaluation of Ca10−xAgx(PO46(OH2 nanoparticles (Ag:HAp-NPs for their antibacterial and antifungal activity. Resistance to antimicrobial agents by pathogenic bacteria has emerged in the recent years and became a major health problem. Here, we report a method for synthesizing Ag doped nanocrystalline hydroxyapatite. A silver-doped nanocrystalline hydroxyapatite was synthesized at 100°C in deionised water. Also, in this paper Ag:HAp-NPs are evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and fungal strains. The specific antimicrobial activity revealed by the qualitative assay is demonstrating that our compounds are interacting differently with the microbial targets, probably due to the differences in the microbial wall structures.

  10. General versus regional anaesthesia for cataract surgery: effects on neutrophil apoptosis and the postoperative pro-inflammatory state.

    LENUS (Irish Health Repository)

    Goto, Y

    2012-02-03

    At clinically relevant concentrations, volatile anaesthetic agents influence neutrophil function. Our hypothesis was that sevoflurane would inhibit neutrophil apoptosis and consequently influence the postoperative pro-inflammatory state. In order to identify selectively the effect of the anaesthetic agent sevoflurane, we studied patients undergoing minimally stimulating (cataract) surgery randomly allocated to receive either sevoflurane (n = 11) or local anaesthesia (n = 12). Venous blood samples were taken immediately prior to anaesthesia and at 1, 8 and 24 h thereafter. The rate of neutrophil apoptosis, plasma concentration of cytokines and differential white cell count were measured. The rates of neutrophil apoptosis and plasma concentrations of IL-1beta, TNF-alpha and IL-8 at each time point were similar in the two groups. IL-6 concentrations increased significantly and to a similar extent compared to preanaesthetic levels at 8 and 24 h. This study demonstrates that sevoflurane does not influence the rate of neutrophil apoptosis, cytokine concentrations and neutrophil count following cataract surgery.

  11. Synthesis of pro-inflammatory cytokines and adhesion molecules expression by the irradiated human monocyte/macrophage

    International Nuclear Information System (INIS)

    As lesions induced by ionizing radiations are essentially noticed in organs the functional and structural organisation of which depend on the highly proliferative stem cell pool, the author reports an in-vivo investigation of the effect of a gamma irradiation on the expression and secretion of pro-inflammatory cytokines par human monocytes/macrophages. In order to study the role of the cell environment in the radiation-induced inflammation, the author studied whether a co-stimulation of monocytes/macrophages by gamma irradiation, or the exposure of co-cultures of monocytes/macrophages and lymphocytes, could modulate the regulation of inflammatory cytokines. The author also studied the modulation of the expression of adhesion molecules mainly expressed by the monocyte/macrophage, and the membrane density of the CD14 receptor after irradiation of monocytes/macrophages during 24 hours, and of totally differentiated macrophages after seven days of culture

  12. Effect of Pulmonary Surfactant on Antimicrobial Activity In Vitro

    OpenAIRE

    Schwameis, R; Erdogan-Yildirim, Z.; Manafi, M.; Zeitlinger, M. A.; Strommer, S.; Sauermann, R.

    2013-01-01

    Time-kill curve experiments were performed with linezolid, doripenem, tigecycline, moxifloxacin, and daptomycin against Staphylococcus aureus and with colistin, moxifloxacin, and doripenem against Pseudomonas aeruginosa to evaluate the effect of porcine pulmonary surfactant on antimicrobial activity. Pulmonary surfactant significantly impaired the activities of moxifloxacin and colistin. When antibiotics are being developed for respiratory tract infections, the method described here might be ...

  13. P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Ricardo A Garcia

    Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

  14. Antimicrobial activity of magnolol and honokiol against periodontopathic microorganisms.

    Science.gov (United States)

    Chang, B; Lee, Y; Ku, Y; Bae, K; Chung, C

    1998-05-01

    Magnolol (1) and honokiol (2), main compounds from the stem bark of Magnolia obovata Thunb., were evaluated for an antimicrobial activity against periodontopathic microorganisms, Porphyromonas gingivalis, Prevotella gingivalis, Actinobacillus actinomycetemcomitans, Capnocytophaga gingivalis, and Veillonella disper, and a cytotoxicity against human gingival fibroblasts and epithelial cells. Our results indicate that magnolol and honokiol, although less potent than chlorhexidine, show a significant antimicrobial activity against these microorganisms, and a relatively low cytotoxic effect on human gingival cells. Thus, it is suggested that magnolol and honokiol may have a potential therapeutic use as a safe oral antiseptic for the prevention and the treatment of periodontal disease. PMID:9619121

  15. Antimicrobial and antioxidant activity of natural honeys of different origin

    Directory of Open Access Journals (Sweden)

    Miartina Fikselová

    2014-11-01

    Full Text Available To examine the antimicrobial and antioxidant activity of 15 natural honeys, honey samples were collected from different locations of Slovakia, Poland and Serbia. For antimicrobial activity determination honey solutions were prepared at three concentrations: 50, 25 and 12.5 % (by mass per volume. The potential antimicrobial activity of  selected samples against four species of bacteria (Escherichia coli CCM 3988, Pseudomonas aeroginosa CCM 1960, Staphylococcus epidermis CCM 4418, Bacillus cereus CCM 2010 and two species of yeasts (Saccharomyces cerevisiae CCM 8191, Candida albicans CCM 8216 was studied using the disc diffusion method. After incubation, the zones of inhibition of the growth of the microorganisms around the disks were measured. The strongest antimicrobial activity was shown at honey samples of 50 % concentration against Escherichia coli, Pseudomonas aeroginosa and Staphylococcus epidermis. Against Saccharomyces cerevisae and Candida albicans very low (at 50 %, 25 % concentration or zero antifugal (at 12.5 % concentration activity was determined. From the results obtained it was shown the variable ability of honey samples to scavenge stable free radical DPPH. TEACDPPH values ranged between 0.1-1.0 mmol.kg-1. As the antioxidative best source buckwheat honey was manifested and the lowest antioxidant activity was shown at acacia honey.

  16. Antioxidant and antimicrobial activities of selected medicinal plants from Algeria

    Institute of Scientific and Technical Information of China (English)

    Krimat Soumia; Dob Tahar; Lamari Lynda; Boumeridja Saida; Chelghoum Chabane; Metidji Hafidha

    2014-01-01

    Objective:To evaluate the antioxidant and antimicrobial activity of methanolic extract extracts of selected Algerian medicinal plants. Methods:Antioxidant activity of extracts was evaluated in terms of radical scavenging potential (2,2-diphenyl-1-picrylhydrazyl) and β-carotene bleaching assay. Total phenolic contents and flavonoid contents were also measured. Antimicrobial activity of these plants was examined against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Results:The values of IC50 ranged from 4.30 μg/mL to 486.6 μg/mL for the DPPH method, while total antioxidant activity using β-carotene/linoleic acid bleaching assay ranged from 17.03%to 86.13%. It was found that Pistacia lentiscus showed the highest antioxidant capacities using DPPH assay (IC50=4.30 μg/mL), while Populus trimula, Origanum glandulosum, Centaurea calcitrapa, Sysimbrium officinalis and Rhamnus alaternus showed the highest percent of total antioxidant activity inβ-carotene/linoleic acid bleaching assay. Total phenolic and flavonoid contents ranged from 3.96 to 259.65 mg GAE/g extract and from 1.13 to 26.84 mg QE/g extract, respectively. The most interesting antimicrobial activity was obtained from Sysimbrium officinalis, Rhamnus alaternus, Origanum glandulosum, Cupressus sempervirens, Pinus halipensis and Centaurea calcitrapa. Conclusions:The results indicated that the plants tested may be potential sources for isolation of natural antioxidant and antimicrobial compounds.

  17. [Isolation and antimicrobial activities of actinomycetes from vermicompost].

    Science.gov (United States)

    Wang, Xue-jun; Yan, Shuang-lin; Min, Chang-li; Yang, Yan

    2015-02-01

    In this paper, actinomycetes were isolated from vermicompost by tablet coating method. Antimicrobial activities of actinomycetes were measured by the agar block method. Strains with high activity were identified based on morphology and biochemical characteristics, as well as 16S rDNA gene sequence analysis. The results showed that 26 strains of actinomycetes were isolated, 16 of them had antimicrobial activities to the test strains which accounts for 61.54% of all strains. Among the 16 strains, the strain QYF12 and QYF22 had higher antimicrobial activity to Micrococcus luteus, with a formed inhibition zone of 27 mm and 31 mm, respectively. While the strain QYF26 had higher antimicrobial activity to Bacillus subtilis, and the inhibition zone diameter was 21 mm. Based on the identification of strains with high activity, the strain QYF12 was identified as Streptomyces chartreusis, the strain QYF22 was S. ossamyceticus and the strain QYF26 was S. gancidicus. This study provided a theoretical basis for further separate antibacterial product used for biological control. PMID:26137678

  18. Antioxidant and antimicrobial activities of selected medicinal plants from Algeria

    Directory of Open Access Journals (Sweden)

    Krimat Soumia

    2014-06-01

    Full Text Available Objective: To evaluate the antioxidant and antimicrobial activity of methanolic extract extracts of selected Algerian medicinal plants. Methods: Antioxidant activity of extracts was evaluated in terms of radical scavenging potential (2,2-diphenyl-1-picrylhydrazyl and β-carotene bleaching assay. Total phenolic contents and flavonoid contents were also measured. Antimicrobial activity of these plants was examined against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Results: The values of IC50 ranged from 4.30 μg/mL to 486.6 μg/mL for the DPPH method, while total antioxidant activity using β-carotene/linoleic acid bleaching assay ranged from 17.03% to 86.13%. It was found that Pistacia lentiscus showed the highest antioxidant capacities using DPPH assay (IC50=4.30 μg/mL, while Populus trimula, Origanum glandulosum, Centaurea calcitrapa, Sysimbrium officinalis and Rhamnus alaternus showed the highest percent of total antioxidant activity in β-carotene/linoleic acid bleaching assay. Total phenolic and flavonoid contents ranged from 3.96 to 259.65 mg GAE/g extract and from 1.13 to 26.84 mg QE/g extract, respectively. The most interesting antimicrobial activity was obtained from Sysimbrium officinalis, Rhamnus alaternus, Origanum glandulosum, Cupressus sempervirens, Pinus halipensis and Centaurea calcitrapa. Conclusions: The results indicated that the plants tested may be potential sources for isolation of natural antioxidant and antimicrobial compounds.

  19. Synthesis and antimicrobial activity of amphiphilic carbohydrate derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Roberta C.N.; Oda, Simone C.; Almeida, Mauro V. de; Le Hyaric, Mireille [Universidade Federal de Juiz de Fora (UFJF), MG (Brazil). Dept. de Quimica]. E-mail: mireille.hyaric@ufjf.edu.br; Lourenco, Maria C.S.; Vicente, Felipe R.C. [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil ). Instituto de Pesquisa Clinica Evandro Chagas (IPEC); Barbosa, Nadia R.; Trevizani, Rafael; Santos, Priscila L.C. [Universidade Federal de Juiz de Fora (UFJF), MG (Brazil). Faculdade de Farmacia e Bioquimica

    2008-07-01

    N-monoalkylated diamines were synthesised and treated with D-ribonolactone or D-gluconolactone. The resulting aldonamides were evaluated for their antimicrobial activity against S. aureus, E. coli, M. tuberculosis and C. albicans. Two hydrazides were also prepared from ribonohydrazide and their biological activity was compared to their amide analogues. All the ribono-derivatives displayed moderated antitubercular activity, and some of them were also active against S. aureus. (author)

  20. ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY ON EMBLICA OFFICINALIS SEED EXTRACT

    OpenAIRE

    Gupta Priya; Nain Parminder; Sidana Jaspreet

    2012-01-01

    The present study was carried out to evaluate in vitro antibacterial and free radical scavenging activity of methanolic extract of Emblica officinalis seed. The antimicrobial activity was assessed against gram positive and gram negative bacteria namely E.coli, P.aeruginosa, K.pneumoniae, S. aureus, Enterococcus by using agar well diffusion method. The antioxidant activity of seed extract was evaluated by using the free radical scavenging activity assay i.e DPPH method, hydrogen peroxide and r...

  1. ANTIMICROBIAL ACTIVITY OF MEDICINAL PLANTS AGAINST DIFFERENT STRAINS OF BACTERIA

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    Alexander Vatľák

    2014-02-01

    Full Text Available In this study, methanolic extracts of Tilia cordata Mill. and Aesculus hippocastanum which had been described in herbal books, were screened for their antimicrobial activity against gramnegative and grampositive bacteria. The following strains of bacteria for antimicrobial activity were used gramnegative bacteria: Escherichia coli CCM 3988, Listeria ivanovii CCM 5884, Listeria innocua CCM 4030, Pseudomonas aeruginosa CCM 1960, Serratia rubidaea CCM 4684 and grampositive bacteria: Brochothrix thermosphacta CCM 4769, Enterococcus raffinosus CCM 4216, Lactobacillus rhamnosus CCM 1828, Paenobacillus larvae CCM 4483 and Staphylococcus epidermis CCM 4418 using disc diffusion method and microbroth dilution technique according to CLSI. Probit analysis was used in this experiment. Of the 2 plant extracts tested, all extracts showed antimicrobial activity against one or more species of microorganisms. The highest antibacterial activity of Tilia cordata and Aesculus hippocastanum methanolic extract was measured against gramnegative bacteria Pseudomonas aeruginosa used with disc diffusion method. The strong antimicrobial activity with microbroth dilution method of Tilia cordata and Aesculus hippocastanum were found against Listeria ivanovii.

  2. Antimicrobial Activity of Bacteriocins and Their Applications

    Science.gov (United States)

    Drosinos, Eleftherios H.; Mataragas, Marios; Paramithiotis, Spiros

    Bacteriocins are peptides or proteins that exert an antimicrobial action against a range of microorganisms. Their production can be related to the antagonism within a certain ecological niche, as the producer strain, being itself immune to its action, generally gains a competitive advantage. Many Gram-positive and Gram-negative microorganisms have been found to produce bacteriocins. The former, and especially the ones produced by lactic acid bacteria, has been the field of intensive research during the last decades mainly due to their properties that account for their suitability in food preservation and the benefits arising from that, and secondarily due to the broader inhibitory spectrum compared to the ones produced by Gramnegative microorganisms.

  3. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    NARCIS (Netherlands)

    Larsen, J.M.; Steen-Jensen, D.B.; Laursen, J.M.; Sondergaard, J.N.; Musavian, H.S.; Butt, T.M.; Brix, S.

    2012-01-01

    Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties o

  4. THE EFFECTS OF ANTI-INFLAMMATORY IFNγ AND PRO-INFLAMMATORY TNFα, IL-1β ON CHEMOKINE RELEASE IN MOUSE EPITHELIAL CELLS

    Science.gov (United States)

    RATIONALE: Asthma is a chronic inflammatory disorder of the airways that affects nearly 20 million individuals in the US. Airway inflammation is a hallmark characteristic of asthma and is the result of numerous pro-inflammatory cytokines such as IL-1β and TNFα . Interestingly...

  5. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.

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    Stephanie J Soscia

    Full Text Available BACKGROUND: The amyloid beta-protein (Abeta is believed to be the key mediator of Alzheimer's disease (AD pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide data supporting an in vivo function for Abeta as an antimicrobial peptide (AMP. Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies. CONCLUSIONS/SIGNIFICANCE: Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.

  6. Antimicrobial activity of kombucha made from Rtanj tea

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    Cvetković Dragoljub D.

    2005-01-01

    Full Text Available Kombucha is a beverage with special therapeutic properties produced by the metabolic activity of yeasts and acetic acid bacteria in sweetened black tea (traditional cultivation medium. The antimicrobial activity of kombucha (for consumption made from black tea and Rtanj tea, as well as particular control samples, was examined by the modified disc diffusion method. Salmonella enteritidis, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa Staphylococcus aureus, Bacillus sp., Sarcina lutea, Penicillium aurantiogriseum, Aspergilus niger, Aspergilus flavus, Rhodotorula sp. Candida pseudotropi-calis and Saccharomyces cerevisae have been used as test organisms. Acetic acid and kombucha samples show significant antimicrobial activity against all bacteria except Sarcina lutea. The other control samples (neutralized kombucha, tea and a "model sistem" show less bacteriostatic activity. Kombucha and acetic acid solution show borderline inhibitory activity against some moulds, while was no activity against yeasts.

  7. The Fat-1 Transgene in Mice Increases Antioxidant Potential, Reduces Pro-Inflammatory Cytokine Levels, and Enhances PPARγ and SIRT-1 Expression on a Calorie Restricted Diet

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    Md Mizanur Rahman

    2009-01-01

    Full Text Available Both n-3 fatty acids (FA and calorie-restriction (CR are known to exert anti-inflammatory and anti-oxidative effects in animals and humans. In this study, we investigated the synergistic anti-inflammatory and anti-oxidative capacity of n-3 FA and CR using Fat-1 transgenic mice (Fat-1 that are capable of converting n-6 FA to n-3 FA endogenously. Wild type (WT and Fat-1 mice were maintained on ad libitum (AL or CR (40% less than AL AIN-93 diet supplemented with 10% corn oil (rich in n-6 FA for 5 months. Significantly lower levels of n-6/n-3 FA ratio were observed in serum, muscle and liver of Fat-1 mice fed AL or CR as compared to that of WT mice fed AL or CR. Muscle catalase (CAT, super oxide dismutase (SOD, glutathione peroxidase (GPX activities, and liver CAT and SOD activities were found higher in Fat-1 mice as compared to that of WT mice. These activities were more pronounced in Fat-1/CR group as compared to other groups. Serum pro-inflammatory markers, such as tumor necrosis factor (TNFα, interleukin (IL-1β and IL-6 were found lower in Fat-1 mice, as compared to that of WT mice. This anti-inflammatory effect was also more pronounced in Fat-1/CR group as compared to that of other groups. Furthermore, significantly higher levels of peroxisome proliferator-activated receptor (PPA Rgamma and life prolonging gene, sirtuin (SIRT-1 expression were found in liver of Fat-1/CR mice, as compared to that of WT/CR mice. These data suggest that n-3 FA along with moderate CR may prolong lifespan by attenuating inflammation and oxidative stress.

  8. The Dietary Isoflavone Daidzein Reduces Expression of Pro-Inflammatory Genes through PPARα/γ and JNK Pathways in Adipocyte and Macrophage Co-Cultures.

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    Yuri Sakamoto

    Full Text Available Obesity-induced inflammation caused by adipocyte-macrophage interactions plays a critical role in developing insulin resistance, and peroxisome proliferator-activated receptors (PPARs regulate inflammatory gene expression in these cells. Recently, the soy isoflavone daidzein was reported to act as a PPAR activator. We examined whether daidzein affected adipocyte-macrophage crosstalk via the regulation of PPARs. Co-cultures of 3T3-L1 adipocytes and RAW264 macrophages, or palmitate-stimulated RAW264 macrophages were treated with daidzein in the presence or absence of specific inhibitors for PPARs: GW6471 (a PPARα antagonist, and GW9662 (a PPARγ antagonist. Inflammatory gene expression was then determined. Daidzein significantly decreased chemokine (C-C motif ligand 2 (Ccl2, known in humans as monocyte chemo-attractant protein 1 (MCP1 and interleukin 6 (Il6 mRNA levels induced by co-culture. In 3T3-L1 adipocytes, daidzein inversed the attenuation of adiponectin gene expression by co-culture, and these effects were inhibited by the PPAR-γ specific inhibitor. Daidzein also decreased Ccl2 and Il6 mRNA levels in RAW264 macrophages stimulated with palmitate or conditioned medium (CM from hypertrophied 3T3-L1 adipocytes. This inhibitory effect on Il6 expression was abrogated by a PPAR-α inhibitor. Additionally, we examined the activation of nuclear factor-kappa B (NF-κB and c-Jun N-terminal kinase (JNK pathways and found that daidzein significantly inhibited palmitate-induced phosphorylation of JNK. Our data suggest that daidzein regulates pro-inflammatory gene expression by activating PPAR-α and -γ and inhibiting the JNK pathway in adipocyte and macrophage co-cultures. These effects might be favorable in improving adipose inflammation, thus, treatment of daidzein may be a therapeutic strategy for chronic inflammation in obese adipose tissue.

  9. Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

    NARCIS (Netherlands)

    de Sousa Pereira Simoes de Melo, Manuel; Ferre, Rafael; Feliu, Lidia; Bardaji, Eduard; Planas, Marta; Castanho, Miguel A. R. B.

    2011-01-01

    Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible co

  10. Antimicrobial and Antifungal Activity of Pelargonium roseum Essential Oils

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    Gâlea Carmen

    2014-12-01

    Conclusion: The volatile oils exhibited considerable inhibitory effects against all the organisms under test, in some cases comparable with those of the reference antibiotics. There were no considerable differences between the antimicrobial activities of the oil obtained by distillation and commercially available Pelargonium oils.

  11. Antimicrobial activity of carvacrol toward Bacillus cereus on rice

    NARCIS (Netherlands)

    Ultee, A.; Slump, R.A.; Steging, G.; Smid, E.J.

    2000-01-01

    The antimicrobial activity of carvacrol, a compound present in the essential oil fraction of oreganum and thyme, toward the foodborne pathogen Bacillus cereus on rice was studied. Carvacrol showed a dose-related inhibition of growth of the pathogen. Concentrations of 0.15 mg/g and higher inhibited t

  12. In vitro antimicrobial activity of mangrove plant Sonneratia alba

    Institute of Scientific and Technical Information of China (English)

    Shahbudin Saad; Muhammad Taher; Deny Susanti; Haitham Qaralleh; Anis Fadhlina Izyani Bt Awang

    2012-01-01

    Objective:To investigate the antimicrobial property of mangrove plant Sonneratia alba (S. alba). Methods: The antimicrobial activity was evaluated using disc diffusion and microdilution methods against six microorganisms. Soxhlet apparatus was used for extraction with a series of solvents, n-hexane, ethyl acetate and methanol in sequence of increasing polarity. Results:Methanol extract appeared to be the most effective extract while n-hexane extract showed no activity. The antimicrobial activities were observed against the gram positive bacteria Staphylococcus aureus (S. aureus) and Bacillus cereus (B. cereus), the gram negative Escherichia coli (E. coli) and the yeast Cryptococcus neoformans. Pseudomonas aeruginosa and Candida albicans appeared to be not sensitive to the concentrations tested since no inhibition zone was observed. E. coli (17.5 mm) appeared to be the most sensitive strain followed by S. aureus (12.5 mm) and B. cereus (12.5 mm). Conclusions:From this study, it can be concluded that S. alba exhibits antimicrobial activities against certain microorganisms.

  13. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species

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    Snežana Marković

    2011-08-01

    Full Text Available The antioxidative, antimicrobial and antiproliferative potentials of the methanol extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic acid equivalent (GA/g of extract and the total flavonoid content from 20.14 to 44.43 mg of rutin equivalent (Ru/g of extract. The antioxidant capacities of the lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH radicals scavenging. Hypogymnia physodes with the highest phenolic content showed the strongest DPPH radical scavenging effect. Further, the antimicrobial potential of the lichen extracts was determined by a microdilution method on 29 microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi and 4 yeast species. A high antimicrobial activity of all the tested extracts was observed with more potent inhibitory effects on the growth of Gram (+ bacteria. The highest antimicrobial activity among lichens was demonstrated by Hypogymnia physodes and Cladonia foliacea. Finally, the antiproliferative activity of the lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116 by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide viability assay and acridine orange/ethidium bromide staining. The methanol extracts of Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than the other extracts. All lichen species showed the ability to induce apoptosis of HCT-116 cells.

  14. Synthesis and Antimicrobial Activities of Some Pyrazoline Derivatives

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    Ganguly Sushmita S

    2012-10-01

    Full Text Available An efficient synthesis of 3, 5-disubstituted-2-pyrazoline was carried out by the condensation of chalcones with hydrazine hydrate in ethanol in presence of piperidine. The newly synthesized compounds were characterized by 1H NMR spectroscopy, IR spectroscopy, MS, elemental analysis and screened for their antimicrobial activity against various strains of bacteria and fungi.

  15. Antimicrobial activity of different endodontic sealers: An in vitro evaluation

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    Saha S

    2010-01-01

    Full Text Available Background: Microbes are considered as the primary etiological agents in endodontic diseases. The ways of reducing these agents are root canal debridement, antimicrobial irrigants, and antibacterial filling materials. But the complexity of the pulp canal system presents a problem for chemomechanical preparation. One of the factors determining the success of endodontic treatment is the sealing material with a potent bactericidal effect. Aim: The aim of the present study was to assess the antimicrobial activity of endodontic sealers of different bases - in vitro. Materials and Method: The antimicrobial activity of three root canal sealers (endomethasone, AH 26, and apexit was evaluated against seven strains of bacteria at various time intervals using the agar diffusion test. The freshly mixed sealers were placed in prepared wells of agar plates inoculated with the test microorganisms. The plates were incubated for 24, 48, 72 hours, and 7 and 15 days. The mean zones of inhibition were measured. Statistical Analysis: All statistical analysis was performed using the SPSS 13 statistical software version. The analysis of variance (ANOVA, post-hoc Bonferroni test, and paired t test were performed to reveal the statistical significance. Results: Statistically significant zones of bacterial growth inhibition were observed in descending order of antimicrobial activity: endomethasone, AH 26, and apexit. Conclusion: Zinc oxide eugenol based root canal sealer produced largest inhibitory zones followed in decreasing order by epoxy resin based sealer and least by calcium hydroxide based root canal sealer.

  16. COW DUNG- A BOON FOR ANTIMICROBIAL ACTIVITY

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    SUSHMITA SHRIVASTAVA*, ALKA MISHRA ARTI PAL

    2014-09-01

    Full Text Available India is an agricultural country having variety of plants and animals. Among the animals, cattle like cow has a prominent place in our country. It is considered as go-mata and worshipped by every hindu of India. The five products of cow called “Panchgavya” is a precious gift of this holy animal to our society, which consist of milk, curd, ghee, urine and dung. Among these, cow dung also called cow pad, is a component having crude protein, cellulose, hemicellulose and minerals. It is an efficient organic manure used to increase plant yield in fields. Cow dung slurry is also used by people of our country for plastering the floors and walls of their houses. Considering this custom of our society, a study had been done to evaluate antibacterial and antifungal properties of cow dung extract in distil water, ethanol and n- hexane against Candida, E. coli, Pseudomonas and Staphylococcus aureus and found it highly effective against these microbes. The study revealed that cow dung extract possess antimicrobial properties, which can be used to fight against certain pathogenic diseases and other ailments.

  17. Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats.

    Science.gov (United States)

    Gnanaraj, Charles; Shah, Muhammad Dawood; Makki, Jaafar Sadeq; Iqbal, Mohammad

    2016-08-01

    Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 ± 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI. PMID:26810847

  18. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways.

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    Muthu K Shanmugam

    Full Text Available Prostate cancer is one of the leading causes of cancer death among men worldwide. In this study, using transgenic adenocarcinoma of mouse prostate (TRAMP mice, the effect of diet enriched with 1% w/w ursolic acid (UA was investigated to evaluate the stage specific chemopreventive activity against prostate cancer. We found that TRAMP mice fed with UA diet for 8 weeks (weeks 4 to 12 delayed formation of prostate intraepithelial neoplasia (PIN. Similarly, mice fed with UA diet for 6 weeks (weeks 12 to 18 inhibited progression of PIN to adenocarcinoma as determined by hematoxylin and eosin staining. Finally, TRAMP mice fed with UA diet for 12 weeks (weeks 24 to 36 demonstrated markedly reduced tumor growth without any significant effects on total body weight and prolonged overall survival. With respect to the molecular mechanism, we found that UA down-regulated activation of various pro-inflammatory mediators including, NF-κB, STAT3, AKT and IKKα/β phosphorylation in the dorsolateral prostate (DLP tissues that correlated with the reduction in serum levels of TNF-α and IL-6. In addition, UA significantly down-regulated the expression levels of cyclin D1 and COX-2 but up-regulated the levels of caspase-3 as revealed by immunohistochemical analysis of tumor tissue sections. Finally, UA was detected in serum samples obtained from various mice groups fed with enriched diet in nanogram quantity indicating that it is well absorbed in the GI tract. Overall, our findings provide strong evidence that UA can be an excellent agent for both the prevention and treatment of prostate cancer.

  19. Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?

    Science.gov (United States)

    2014-01-01

    Background Both active and passive tobacco smoke (TS) potentially impair the vascular endothelial function in a causative and dose-dependent manner, largely related to the content of reactive oxygen species (ROS), nicotine, and pro-inflammatory activity. Together these factors can compromise the restrictive properties of the blood–brain barrier (BBB) and trigger the pathogenesis/progression of several neurological disorders including silent cerebral infarction, stroke, multiple sclerosis and Alzheimer’s disease. Based on these premises, we analyzed and assessed the toxic impact of smoke extract from a range of tobacco products (with varying levels of nicotine) on brain microvascular endothelial cell line (hCMEC/D3), a well characterized human BBB model. Results Initial profiling of TS showed a significant release of reactive oxygen (ROS) and reactive nitrogen species (RNS) in full flavor, nicotine-free (NF, “reduced-exposure” brand) and ultralow nicotine products. This release correlated with increased oxidative cell damage. In parallel, membrane expression of endothelial tight junction proteins ZO-1 and occludin were significantly down-regulated suggesting the impairment of barrier function. Expression of VE-cadherin and claudin-5 were also increased by the ultralow or nicotine free tobacco smoke extract. TS extract from these cigarettes also induced an inflammatory response in BBB ECs as demonstrated by increased IL-6 and MMP-2 levels and up-regulation of vascular adhesion molecules, such as VCAM-1 and PECAM-1. Conclusions In summary, our results indicate that NF and ultralow nicotine cigarettes are potentially more harmful to the BBB endothelium than regular tobacco products. In addition, this study demonstrates that the TS-induced toxicity at BBB ECs is strongly correlated to the TAR and NO levels in the cigarettes rather than the nicotine content. PMID:24755281

  20. Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model.

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    Anna A De Boer

    Full Text Available Paracrine interactions between adipocytes and macrophages contribute to chronic inflammation in obese adipose tissue. Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA and eicosapentaenoic (EPA acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism, with 125 µM of albumin-complexed DHA, EPA, palmitic acid (PA, or albumin alone (control. Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907 in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p ≤ 0.05 with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p<0.05 of Mcp1 (-7.1 fold and increased expression of the negative regulator, Mcp1-IP (+1.5 fold. In macrophages, DHA decreased mRNA expression of pro-inflammatory M1 polarization markers (p ≤ 0.05, Nos2 (iNOS; -7 fold, Tnfα (-4.2 fold and Nfκb (-2.3 fold, while increasing anti-inflammatory Tgfβ1 (+1.7 fold. Interestingly, the PPARγ antagonist co-administered with DHA or EPA in co-culture reduced (p ≤ 0.05 adiponectin cellular protein, without modulating other cytokines (protein or mRNA. Overall, our findings suggest that DHA may lessen the degree of MCP1 and IL-6 secreted from adipocytes, and may reduce the degree of M1 polarization of macrophages recruited to adipose tissue, thereby decreasing the intensity of pro-inflammatory cross-talk between adipocytes

  1. Selection for pro-inflammatory mediators produces chickens more resistant to Clostridium perfringens-induced necrotic enteritis.

    Science.gov (United States)

    Swaggerty, C L; McReynolds, J L; Byrd, J A; Pevzner, I Y; Duke, S E; Genovese, K J; He, H; Kogut, M H

    2016-02-01

    We developed a novel selection method based on an inherently high and low phenotype of pro-inflammatory mediators and produced "high" and "low" line chickens. We have shown high line birds are more resistant to Salmonella enterica serovar Enteritidis and Eimeria tenella compared to the low line. Clostridium perfringens is the fourth leading cause of bacterial-induced foodborne illness, and is also an economically important poultry pathogen and known etiologic agent of necrotic enteritis (NE). The objective of this study was to determine if high line birds were also more resistant to NE than low line birds using an established model. Birds were reared in floor pens and challenges were conducted twice (high line = 25/trial, 50 birds total; low line = 26/trial, 52 birds total). Day-old chicks were provided a 55% wheat-corn-based un-medicated starter diet. A bursal disease vaccine was administered at 10× the recommended dose via the ocular route at 14-d-of-age. Birds were challenged daily for 3 d beginning at 16-d-of-age by oral gavage (3 mL) with 10(7) colony forming units (cfu) of C. perfringens/mL then necropsied at 21-d-of-age. All birds had sections of the intestine examined and scored for lesions while the first 10 necropsied also had gut content collected for C. perfringens enumeration. Chickens from the high line were more resistant to C. perfringens-induced NE pathology compared to the low line, as indicated by reduced lesion scores. Ninety percent of the high line birds had lesions of zero or one compared to 67% of the low line birds. Wilcoxon rank sum test showed significantly higher lesion scores in the low line birds compared to the high line (P < 0.0001). There were no differences in the C. perfringens recovered (P = 0.83). These data provide additional validation and support selection based on elevated levels of pro-inflammatory mediators produces chickens with increased resistance against foodborne and poultry pathogens.

  2. Soluble heparan sulfate fragments generated by heparanase trigger the release of pro-inflammatory cytokines through TLR-4.

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    Katharine J Goodall

    Full Text Available Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate (HS, facilitating degradation of the extracellular matrix (ECM and the release of HS-bound biomolecules including cytokines. The remodeling of the ECM by heparanase is important for various physiological and pathological processes, including inflammation, wound healing, tumour angiogenesis and metastasis. Although heparanase has been proposed to facilitate leukocyte migration through degradation of the ECM, its role in inflammation by regulating the expression and release of cytokines has not been fully defined. In this study, the role of heparanase in regulating the expression and release of cytokines from human and murine immune cells was examined. Human peripheral blood mononuclear cells treated ex vivo with heparanase resulted in the release of a range of pro-inflammatory cytokines including IL-1β, IL-6, IL-8, IL-10 and TNF. In addition, mouse splenocytes treated ex vivo with heparanase resulted in the release of IL-6, MCP-1 and TNF. A similar pattern of cytokine release was also observed when cells were treated with soluble HS. Furthermore, heparanase-induced cytokine release was abolished by enzymatic-inhibitors of heparanase, suggesting this process is mediated via the enzymatic release of cell surface HS fragments. As soluble HS can signal through the Toll-like receptor (TLR pathway, heparanase may promote the upregulation of cytokines through the generation of heparanase-cleaved fragments of HS. In support of this hypothesis, mouse spleen cells lacking the key TLR adaptor molecule MyD88 demonstrated an abolition of cytokine release after heparanase stimulation. Furthermore, TLR4-deficient spleen cells showed reduced cytokine release in response to heparanase treatment, suggesting that TLR4 is involved in this response. Consistent with these observations, the pathway involved in cytokine upregulation was identified as being NF-κB-dependent. These data identify a new

  3. Antimicrobial and cytotoxic activities of Abroma augusta Lnn. leaves extract

    Institute of Scientific and Technical Information of China (English)

    FK Saikot; Alam Khan; MF Hasan

    2012-01-01

    Objective: To evaluate the antimicrobial and cytotoxic activity of acetone extract of leaves ofAbroma augusta. Methods: Disc diffusion method was used to demonstrate antibacterial and antifungal activities. Cytotoxicity was determined against brine shrimp nauplii. In addition, minimum inhibitory concentration (MIC) was determined using serial dilution technique to determine antibacterial potency. Results: The extract showed significant antibacterial activities against three gram-positive (Bacillus subtilis, Bacillus megaterium and Staphylococcus aureus) and four gram-negative (Escherichia coli, Shigella dysenteriae, Shigella sonnei and Salmonella typhi) bacteria. The antifungal activity was found strong against five fungi (Aspergillus flavus, Aspergillus niger, Candida albicans, Rhizopus oryzae and Aspergillus fumigatus). In cytotoxicity determination, LC50 of the extract against brine shrimp nauplii was 7.06μg/ml. Conclusions: The Abroma leaves extract may be consider as a potent antimicrobial and cytotoxic agent for further advance research.

  4. Antimicrobial activity of Iranian propolis and its chemical composition

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    Yaghoubi M.J.

    2007-04-01

    Full Text Available The objective of this study was to investigate the antimicrobial activity of ethanol extract of Iranian propolis on some microorganisms using disc diffusion method. The chemical composition of the propolis was also investigated using thin layer chromatography and spectrophotometric methods. Ethanol extract of propolis showed activity only against Gram-positives and fungi, whereas no activity was observed against Gram-negatives. Thin layer chromatography screening revealed the presence of pinocembrine, caffeic acid, kaempferol, phenethyl caffeate, chrysin, and galangin in Iranian propolis. The total flavonoid and phenolic contents were 7.3% and 36%, respectively, which suggests that the strong antimicrobial activity of Iranian propolis may be due to high levels of phenolic and flavonoid compounds.

  5. PHYTOCHEMICAL ANALYSIS AND ANTIMICROBIAL ACTIVITY OF CASIA OCCIDENTALIS (L

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    Venkanna Lunavath

    2013-02-01

    Full Text Available The trend of using natural products has increased and the active plant extracts are frequently screened for new drug discoveries. The present study deals with the screening of Casia occidentalis leaves for their antimicrobial activity against various strains of bacteria. Plant Cassia occidentalis belongs to family Caesalpiniaceae, is a diffuse offensively odorous under shrub. Casia occidentalis were shade dried, powered and was extracted using solvents Methanol. The antimicrobial activity test performed by the disc diffusion method. Preliminary phytochemical analysis of the plant extracts fractions of HXF, CTF, CFF and AQF showed the presence of carbohydrates, amino acids, phytosterols, fixed oils and phenolic compounds. The AQF fraction of C. occidentalis showed high activity across pseudomonas aeuruginosa and staphylococcus aureus bacteria. The present study indicates the potential usefulness of Casia occidentalis leaves in the treatment of various diseases caused by micro-organisms.

  6. Study of the nanomaterials and their antimicrobial activities

    Science.gov (United States)

    Ramadi, Muntaha

    In the last decade, the world faced huge problems associated with the spread of antimicrobial resistant infections that are essentially untreatable such as methicillin resistant Staphylococcus aureus (MRSA) infection. These infections have begun to occur in both hospital and community environments. Developing new antimicrobial surface coatings can hold a great promise to minimize and control various problems that associated with the spreading of infections and biofilms formation, these coatings can be used in medicine where medical devices associated with severe infections, in construction industry and the in food packaging industry. It has been established that single-walled CNTs exhibit a strong antimicrobial activity and can pierce bacterial cell walls. Recently, nanomaterial structures that made from pure carbon such as CNTs have been seen as promising candidates for many potential applications in Biotechnology and bioscience due to the combination of their extraordinary properties that arise from surface area, light weight, strength, flexibility, unique electrical conductivity and many more novel physical and chemical properties at nanoscale level. CNTs have been used widely in biomedical field including drug delivery, gene therapy and creating new biomedical devices with novel properties. Researchers have now made a first step to add carbon nanotubes to antimicrobial agents list. There are two types of CNTs have been used in biomedical research. The first one is a single-walled carbon nanotube (SWNT) and the second is a multi-walled carbon nanotube (MWNT). Recent in vitro studies suggest that carbon nanotubes have antimicrobial activity and coating CNTs with nickel nanoparticle could enhance the antimicrobial activity of cabon nanotubes. In order to test this hypothesis, nickel nanoparticles were deposited on carbon nanotubes (CNTs) by electrochemical deposition. The carbon nanotubes used in this study were XD-CNTs, SWNTs and Ni-coated CNTs. The structure and

  7. Antimicrobial activity of methanol extracts of four Parmeliaceae lichen species

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    Stojanović Igor

    2013-01-01

    Full Text Available Antimicrobial activity of methanol extracts of four Parmeliaceae lichens (Hypogymnia physodes (L. Nyl., Evernia prunastri (L. Ach., Flavoparmelia caperata (L. Hale and Parmelia sulcata Taylor against a panel of microbial strains (11 Gram-positive (Enterococus sp., Bacillus subtilllis, Sarcina lutea, Micrococus luteus, Staphylococcus aureus, Clostridium sporogenes and Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Salmonela enteritidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, the filamentous fungus A. niger and the yeast C. albicans was assayed using a disk diffusion method (1 mg of the extract per disc; extracts were dissolved in methanol, 25 mg/mL. All tested extracts showed moderate antimicrobial activity. Multivariate statistical treatment (agglomerative hierarchical clustering analysis, AHC of the obtained results allowed grouping of the samples according to their antimicrobial potential against different strains: antimicrobial profile of H. physodes and E. prunastri extracts were comparable; the similar is true for F. caperata and P. sulcata samples. In addition, based on the similarities/ dissimilarities in their susceptibility toward the tested extracts, two groups of microorganisms could be distinguished: Group I - P. vulgaris, K. pneumoniae (Gram-negative bacteria, A. niger and C. albicans; Group II - E. coli, S. enteritidis, P. aeruginosa (Gram-negative bacteria and all of the assayed Gram-positive strains. [Projekat Ministarstva nauke Republike Srbije, br. 172044

  8. Production and characterization of antimicrobial active substance from Spirulina platensis.

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    Mostafa M El-Sheekh

    2014-04-01

    Full Text Available The present work was carried out to investigate the ability of Spirulina platensis to produce antimicrobial substance against bacteria and fungi.The cells of the cyanobacterium were subjected to different extractions and the purified antagonistic compound proved to be effective against broad spectrum of bacteria and fungi. The antagonistic compound was purified using thin layer chromatography.The results indicated that the IR spectrum showed bands at 1269 cm(-1, 1414 cm(-1 (C-O-C, 1643 cm(-1 (CO of amide,1563 cm(-1 (C = C and broad band 3441 cm(-1 (of OH and NH., (1HNMR showed δ 0.8 (-CH3, δ 1.2 (-CH2, δ 4.2(-OH, δ 7.2(-NH, δ 7.4 and δ 7.7 (aromatic CH., Mass spectrum showed molecular ion beak at m/z = 341 (abundance (0.03%. Also, the elemental analysis gave molecular formula,C15H18NO8.The purified antimicrobial compound produced by S. platensis was more active against Gram positive, Gram negative bacteria and unicellular fungi, C. albicans. The highest biological activity was recorded against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Aspergillus niger. The results of this investigation proved that cyanobacteria could be a good source for production of antimicrobial agents which could be effective when compared with contemporary antimicrobial compounds.

  9. Antimicrobial activity in vitro of plumbagin isolated from Plumbago species

    OpenAIRE

    Selma Ribeiro de Paiva; Maria Raquel Figueiredo; Tânia Verônica Aragão; Maria Auxiliadora Coelho Kaplan

    2003-01-01

    Plumbagin is a naturally occurring naphthoquinone isolated from roots of Plumbago scandens. The plant was collected at the Campus of Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. P. scandens is used as a traditional medicine for the treatment of several diseases. The antimicrobial activity of plumbagin was evaluated using the macrodilution method. The compound exhibited relatively specific activity against bacteria and yeast. The minimum inhibitory concentration test showed the growth inhibi...

  10. Antimicrobial, antioxidant, and antimutagenic activities of Gladiolus illyricus.

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    Burcu Basgedik

    2014-08-01

    Full Text Available Context: In the present study, the ethanolic extracts of the aerial parts and the rhizomes of G. illyricus were obtained. Aims: To determine the antimicrobial, antioxidant, and antimutagenic properties of G. illyricus extracts. Methods: The antimicrobial activity was studied with the disc diffusion method and the antioxidant capacity by inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH radical and the total antioxidant activity. The antimutagenic activity was investigated by Ames Salmonella/microsome mutagenic test. The bacterial mutant strains Salmonella typhimurium TA98 and TA100 were used to determine antigenotoxic potentials of the extracts. Results: The ethanolic extracts of the aerial parts and the rhizomes showed moderate antimicrobial activity only on Bacillus subtilis. The IC50 value for DPPH radical of the aerial parts and rhizomes were 57.1 ± 1.3 and 48.1 ± 1.1 mg/mL, respectively. The total antioxidant activities of the aerial parts and the rhizomes of G. illyricus at 3.15 mg/mL concentration were 92.3 ± 1.4% and 91.5 ± 2.1%, respectively. These extracts showed antimutagenic effects at 0.5 and 5 mg/plate concentrations. Conclusions: To our knowledge, this is the first study on antimicrobial, antioxidant, and antimutagenic activity of the ethanolic extracts of the aerial parts and the rhizomes from G. illyricus. Our results indicate that the used of these extracts would exert several beneficial effects by virtue of their antioxidant and antimutagenic activities. These activities could be an important topic in the medical and cosmetic fields.

  11. ANTIMICROBIAL ACTIVITY OF THE FRUIT-SEEDS MADHUCA LONGIFOLIA (KOENIG)

    OpenAIRE

    Chirantan S Chakma

    2011-01-01

    The investigation was carried out to study the antibacterial activity of the Madhuca longifolia(Koenig) in gram positive and gram negative organism.. Antimicrobial activity of the acetone and aqueous extracts of M.longifolia were determined against various pathogenic bacteria. The extracts were tested against various bacteria like Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginos, .E.coli by disk diffusion method. Minimum Inhibitory Concentration (MIC) values of both extracts we...

  12. Antioxidant and antimicrobial activity of Turkish endemic Sonchus erzincanicus extracts

    OpenAIRE

    MAVİ, Ahmet; YİĞİT, Nimet; YİĞİT, DEMET; KANDEMİR, Ali

    2011-01-01

    Sonchus erzincanicus (Asteraceae) is a plant species that is endemic to Turkey and grows in Erzincan. Lipid peroxidation inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and total phenolic content of the methanol and water extracts of the plant were determined. Antimicrobial activity of the extracts was also tested against 107 clinical isolates of human pathogenic microorganism strains belonging to Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Pseud...

  13. STUDIES ON THE EFFICACY OF ALOE VERA ON ANTIMICROBIAL ACTIVITY

    OpenAIRE

    T.Karpagam; R. Aruna Devaraj

    2011-01-01

    The aqueous, ethanolic, methanolic, petroleum ether and acetone extracts of Aloe vera were screened for anti-microbial activity using the Minimal Inhibitory Concentration (MIC) method. They were tested against five bacteria (Escherischia coli, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumonia and Staphylococcus aureus). The susceptibility of the microorganisms to the extracts in different concentrations plants were compared. The active component in the extract was determined us...

  14. ANTIMICROBIAL ACTIVITY OF PERICARP EXTRACT OF GARCINIA MANGOSTANA LINN.

    OpenAIRE

    Vishnu Priya V; Mallika Jainu; Surapaneni Krishna Mohan; Saraswathi P,; Chandra Sada Gopan V S

    2010-01-01

    Garcinia mangostana Linn is used as a phytomedicine in South East Asia for the treatment of trauma, diahorrea and skin infections. In the present study anti microbial activity of Garcinia mangostana extract powder was carried out. Antimicrobial activity was examined by determining the minimal inhibitory concentration (MIC) using macrodilution broth technique. Garcinia mangostana extract powder at different concentrations were tested against Staphylococcus aureus, Staphylococcus albus, Microco...

  15. ANTIMICROBIAL ACTIVITY OF PERICARP EXTRACT OF GARCINIA MANGOSTANA LINN.

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    Vishnu Priya V

    2010-09-01

    Full Text Available Garcinia mangostana Linn is used as a phytomedicine in South East Asia for the treatment of trauma, diahorrea and skin infections. In the present study anti microbial activity of Garcinia mangostana extract powder was carried out. Antimicrobial activity was examined by determining the minimal inhibitory concentration (MIC using macrodilution broth technique. Garcinia mangostana extract powder at different concentrations were tested against Staphylococcus aureus, Staphylococcus albus, Micrococcus lutus.

  16. In Vitro Antimicrobial and Antiproliferative Activity of Amphipterygium adstringens

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    A. Rodriguez-Garcia

    2015-01-01

    Full Text Available Amphipterygium adstringens is a plant widely used in Mexican traditional medicine for its known anti-inflammatory and antiulcer properties. In this work, we evaluated the in vitro antimicrobial and antiproliferative activities of the methanolic extract of A. adstringens against oral pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Candida albicans, and Candida dubliniensis, using microdilution (MIC and agar diffusion methods (MBC, and the antiproliferative activity evaluating total growth inhibition (TGI by staining the protein content with sulforhodamine B (SRB, using nine human cancer cell lines. Crude extract (CE of A. adstringens showed some degree of activity against one or more of the strains with a MIC from 0.125 mg/mL to 63 mg/mL and MBC from 1.6 to 6.3 mg/mL and cytotoxic activity, particularly against NCI-ADR/RES, an ovarian cell line expressing multiple resistance drugs phenotype. The CE is a complex mixture of possible multitarget metabolites that could be responsible for both antimicrobial and antiproliferative activities, and further investigation is required to elucidate the identity of active compounds. Nevertheless the CE itself is useful in the development of new antimicrobial treatment based on natural products to prevent oral diseases and as alternative natural source for cancer treatment and prevention.

  17. Anti-Inflammatory and Antimicrobial activity of Flacourtia Ramontchi Leaves

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    Sulbha Lalsare

    2011-06-01

    Full Text Available The literature survey revealed that a very merge amount of pharmacological work has been carried out on Flacourtia ramontchi. Also it was observed from the Ayurvedic literature and Ethnobotanical studies that the plant is very useful in treating inflammation and infectious diseases but no scientific investigation has been done in such direction. Very merge work has been done regarding phytochemical and pharmacological effectiveness on this plant. Successive extraction of the leaves with solvents of increasing polarity; preliminary phytochemical studies of different extracts; screening of chloroform, methanol and hydromethanolic extracts for anti-inflammatory (by Carrageenan induced rat paw model and antimicrobial activity (by Cup and plate method and thin layer chromatographic studies of active extracts using mobile phase i.e. chloroform and methanol. The results clearly indicate that all three extracts i.e. chloroform, methanol and hydromethanolic, of the leaves having anti-inflammatory activity. But the chloroform and methano extract showed promising results and even chloroform extract at the dose 150mg/kg exhibits equipotent anti-inflammatory activity as that of the standard Indomethacin. Methanol extract possess broad-spectrum antimicrobial activity at concentration 10000 mg/ml whereas hydromethanolic and chloroform extracts having more or less antimicrobial activity.

  18. Antioxidant, Antimicrobial Activity and Toxicity Test of Pilea microphylla

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    Amir Modarresi Chahardehi

    2010-01-01

    Full Text Available A total of 9 plant extracts were tested, using two different kinds of extracting methods to evaluate the antioxidant and antimicrobial activities from Pilea microphylla (Urticaceae family and including toxicity test. Antioxidant activity were tested by using DPPH free radical scavenging, also total phenolic contents and total flavonoid contents were determined. Toxicity assay carried out by using brine shrimps. Methanol extract of method I (ME I showed the highest antioxidant activity at 69.51±1.03. Chloroform extract of method I (CE I showed the highest total phenolic contents at 72.10±0.71 and chloroform extract of method II (CE II showed the highest total flavonoid contents at 60.14±0.33. The antimicrobial activity of Pilea microphylla extract was tested in vitro by using disc diffusion method and minimum inhibitory concentration (MIC. The Pilea microphylla extract showed antibacterial activity against some Gram negative and positive bacteria. The extracts did not exhibit antifungal and antiyeast activity. The hexane extract of method I (HE I was not toxic against brine shrimp (LC50 value was 3880 μg/ml. Therefore, the extracts could be suitable as antimicrobial and antioxidative agents in food industry.

  19. Quartz-Containing Ceramic Dusts: In vitro screening of the cytotoxic, genotoxic and pro-inflammatory potential of 5 factory samples

    Science.gov (United States)

    Ziemann, C.; Jackson, P.; Brown, R.; Attik, G.; Rihn, B. H.; Creutzenberg, O.

    2009-02-01

    Inhalation of some respirable crystalline silica (MMAD assay), genotoxicity (Comet-assay) and pro-inflammatory potential (PGE2-liberation, TNF-a mRNA expression) of 5 respirable quartz-containing dusts from ceramic plants: brickwork (BR: 7.8% quartz), tableware granulate/cast (TG/TC: 5.8%/3.1%), tiles (TI: 8.1%), refractory (RF: 3.7%). DQ12 (87% a-quartz) and Al2O3 were used as particulate positive and negative controls, respectively. Primary rat alveolar macrophages and the macrophage cell line NR8383 served as model systems. Aluminium lactate was used as inhibitor of biologically active silica, enabling differentiation of silica- and non-specific toxicity. At 200μg/cm2 (2h) the dusts did not alter significantly LDH-release (except TC), whereas the MTT-assay demonstrated the mainly quartz-independent rank order: DQ12>RF>TG>Ti>BR>TC>Al2O3. DNA-damage was maximal for BR and TI followed by DQ12>TG>TC>RF>Al2O3. All dusts induced PGE2-liberation (DQ12>BR>TC>TG>Ti>RF>Al2O3) at 50μg/cm2 (4h), but TNF-a mRNA (10μg/cm2, 24h) was only increased by DQ12, TG (quartz-dependently), and TC. In conclusion, these in vitro tests were an adequate approach to screen the toxic potential of quartz-containing ceramic dusts, but the quartz-content was too low to differentiate the various quartz-varieties.

  20. Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody.

    Science.gov (United States)

    Oh, Y-H; Jeong, S-R; Kim, J-H; Song, K-J; Kim, K; Park, S; Sohn, S; Shin, H-J

    2005-12-01

    Naegleria fowleri, a free-living amoeba, causes fatal primary amoebic meningoencephalitis in experimental animals and humans. The nfa1 gene (360 bp) was previously cloned from a cDNA library of pathogenic N. fowleri by immunoscreening, and produced a 13.1-kDa recombinant protein that showed pseudopodia-specific localization by immunocytochemistry. On the basis of an idea that the pseudopodia-specific Nfa1 protein seems to be involved in the pathogenicity of N. fowleri, the cytopathic activity of N. fowleri trophozoites co-cultured with rat microglial cells was observed, and the effects of an anti-Nfa1 antibody in a co-culture system were elucidated. Using light, scanning and transmission electron microscopy, it was seen that N. fowleri trophozoites in contact with microglial cells produced vigorous pseudopodia and a food-cup structure. Microglial cells were destroyed by N. fowleri trophozoites as seen from necrotic cell death in a time-dependent manner. In a(51)Cr release assay, N. fowleri showed 17.8%, 24.9%, 54.6% and 98% cytotoxicity against microglial cells at 3, 6, 12 and 24 h post-incubation, respectively. However, when anti-Nfa1 antibody was added in a coculture system, N. fowleri cytotoxicity was reduced to 15.5%, 20.3%, 46.7% and 66.9%, respectively. Moreover, microglial cells co-cultured with N. fowleri trophozoites secreted the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. In the presence of anti-Nfa1 antibody, the secretion of TNF-alpha was slightly, but not significantly, decreased.

  1. Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis.

    Science.gov (United States)

    Xu, Linhao; Shen, Peiqiang; Bi, Yanli; Chen, Jian; Xiao, Zhangang; Zhang, Xiaoming; Wang, Zheng

    2016-09-01

    Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-β1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ-induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IκB/NF-κB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation. In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression. PMID:27355131

  2. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes - A role for the transcription factor NFAT and phosphodiesterase 3B

    Energy Technology Data Exchange (ETDEWEB)

    Omar, Bilal [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden); Banke, Elin, E-mail: elin.banke@med.lu.se [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden); Guirguis, Emilia [Cardiovascular Pulmonary Branch, NHLBI, NIH, Bethesda, MD (United States); Aakesson, Lina [Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Clinical Research Centre, Lund University, Malmoe (Sweden); Manganiello, Vincent [Cardiovascular Pulmonary Branch, NHLBI, NIH, Bethesda, MD (United States); Lyssenko, Valeriya; Groop, Leif [Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmoe (Sweden); Gomez, Maria F. [Department of Clinical Sciences, Vascular ET Coupling, Clinical Research Centre, Lund University, Malmoe (Sweden); Degerman, Eva [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. Black-Right-Pointing-Pointer GIP-induced osteopontin expression is NFAT-dependent. Black-Right-Pointing-Pointer Osteopontin expression is PDE3-dependent. Black-Right-Pointing-Pointer Osteopontin expression is increased in PDE3B KO mice. -- Abstract: The incretin - glucose-dependent insulinotropic polypeptide (GIP) - and the pro-inflammatory cytokine osteopontin are known to have important roles in the regulation of adipose tissue functions. In this work we show that GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. The GIP-induced increase in osteopontin expression was inhibited by the NFAT (the transcription factor nuclear factor of activated T-cells) inhibitor A-285222. Also, the NFAT kinase glycogen synthase kinase (GSK) 3 was upregulated by GIP. To test whether cAMP might be involved in GIP-mediated effects on osteopontin a number of strategies were used. Thus, the {beta}3-adrenergic receptor agonist CL316,243 stimulated osteopontin expression, an effects which was mimicked by OPC3911, a specific inhibitor of phosphodiesterase 3. Furthermore, treatment of phosphodiesterase 3B knock-out mice with CL316,243 resulted in a dramatic upregulation of osteopontin in adipose tissue which was not the case in wild-type mice. In summary, we delineate mechanisms by which GIP stimulates osteopontin in adipocytes. Given the established link between osteopontin and insulin resistance, our data suggest that GIP by stimulating osteopontin expression, also could promote insulin resistance in adipocytes.

  3. Vitamin E metabolite 13'-carboxychromanols inhibit pro-inflammatory enzymes, induce apoptosis and autophagy in human cancer cells by modulating sphingolipids and suppress colon tumor development in mice.

    Science.gov (United States)

    Jang, Yumi; Park, Na-Young; Rostgaard-Hansen, Agnetha Linn; Huang, Jianjie; Jiang, Qing

    2016-06-01

    Vitamin E forms are substantially metabolized to various carboxychromanols including 13'-carboxychromanols (13'-COOHs) that are found at high levels in feces. However, there is limited knowledge about functions of these metabolites. Here we studied δT-13'-COOH and δTE-13'-COOH, which are metabolites of δ-tocopherol and δ-tocotrienol, respectively. δTE-13'-COOH is also a natural constituent of a traditional medicine Garcinia Kola. Both 13'-COOHs are much stronger than tocopherols in inhibition of pro-inflammatory and cancer promoting cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and in induction of apoptosis and autophagy in colon cancer cells. The anticancer effects by 13'-COOHs appeared to be partially independent of inhibition of COX-2/5-LOX. Using liquid chromatography tandem mass spectrometry, we found that 13'-COOHs increased intracellular dihydrosphingosine and dihydroceramides after short-time incubation in HCT-116 cells, and enhanced ceramides while decreased sphingomyelins during prolonged treatment. Modulation of sphingolipids by 13'-COOHs was observed prior to or coinciding with biochemical manifestation of cell death. Pharmaceutically blocking the increase of these sphingolipids partially counteracted 13'-COOH-induced cell death. Further, 13'-COOH inhibited dihydroceramide desaturase without affecting the protein expression. In agreement with these mechanistic findings, δTE-13'-COOH significantly suppressed the growth and multiplicity of colon tumor in mice. Our study demonstrates that 13'-COOHs have anti-inflammatory and anticancer activities, may contribute to in vivo anticancer effect of vitamin E forms and are promising novel cancer prevention agents. PMID:27016075

  4. Antimicrobial activity of chicken NK-lysin against Eimeria sporozoites.

    Science.gov (United States)

    Hong, Yeong H; Lillehoj, Hyun S; Siragusa, Gregory R; Bannerman, Douglas D; Lillehoj, Erik P

    2008-06-01

    NK-lysin is an antimicrobial and antitumor polypeptide that is considered to play an important role in innate immunity. Chicken NK-lysin is a member of the saposin-like protein family and exhibits potent antitumor cell activity. To evaluate the antimicrobial properties of chicken NK-lysin, we examined its ability to reduce the viability of various bacterial strains and two species of Eimeria parasites. Culture supernatants from COS7 cells transfected with a chicken NK-lysin cDNA and His-tagged purified NK-lysin from the transfected cells both showed high cytotoxic activity against Eimeria acervulina and Eimeria maxima sporozoites. In contrast, no bactericidal activity was observed. Further studies using synthetic peptides derived from NK-lysin may be useful for pharmaceutical and agricultural uses in the food animal industry.

  5. Antimicrobial and cytotoxic activities of Tripleurospermum parviflorum (Willd. Pobed

    Directory of Open Access Journals (Sweden)

    Tuğçe Fafal Erdoğ an

    2013-01-01

    Full Text Available The antimicrobial and cytotoxic activities of n-hexane, methanol, ethanol, ethylacetate and water extracts ofTripleurospermum parviflorum(Willd. Pobed. were evaluatedin this study. The antimicrobial activities of the extracts were reported againstEscherichia coli ATCC 29998,Escherichia coli ATCC 25922,Escherichia coli ATCC 11230,Staphylococcus aureus ATCC 6538P,Staphylococcus aureus ATCC 29213,Enterobacter cloacae ATCC 13047, Enterococcus faecalis ATCC 29212,Pseudomonas aeroginosa ATCC 27853 as bacteria and Candida albicansATCC 10239 as yeastlike fungi by disc diffusion method. Cytotoxicactivity of the extracts was tested in vitro against Brine shrimp. All of the extracts showed a range of activity against the tested bacteria and brine shrimp

  6. Synthesis and antimicrobial activity of some novel fused heterocyclic moieties

    Directory of Open Access Journals (Sweden)

    Nareshvarma Seelam

    2013-06-01

    Full Text Available Since the discovery of heterocyclic moieties the chemistry of 1,3,4-thiadiazole and their fused compounds continue to draw attention of organic chemists due to their various biological activities. Here a new class of 1, 3, 4-thiadiazoles which are incorporating with isoxazolo-thiazole moieties were synthesized by the reaction of chalcone derivatives of [ 1, 3, 4 ] thiadiazol-2-yl-thiazolidin-4-one with hydroxylamine hydrochloride. The chemical structures of these compounds were confirmed by IR, NMR ( 1H & 13C and mass spectral studies. The new synthesized compounds were evaluated for their antimicrobial activity. The final results revealed that some of the compounds were exhibited well antimicrobial activity compared to the standard drugs.

  7. N(6)-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways.

    Science.gov (United States)

    Lu, Meng-Ying; Chen, Chin-Chu; Lee, Li-Ya; Lin, Ting-Wei; Kuo, Chia-Feng

    2015-10-23

    Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N(6)-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca(2+) antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom. PMID:26394068

  8. In Vitro Antimicrobial Bioassays, DPPH Radical Scavenging Activity, and FTIR Spectroscopy Analysis of Heliotropium bacciferum

    OpenAIRE

    Ahmad, Sohail; AbdEl-Salam, Naser M.; Ullah, Riaz

    2016-01-01

    The present study deals with the antimicrobial, antioxidant, and functional group analysis of Heliotropium bacciferum extracts. Disc diffusion susceptibility method was followed for antimicrobial assessment. Noteworthy antimicrobial activities were recorded by various plant extracts against antibiotic resistant microorganisms. Plant flower extracts antioxidant activity was investigated against 2, 2-diphenyl-1-picryl hydrazyl radical by ultraviolet spectrophotometer (517 nm). Plant extracts di...

  9. Design and characterization of an acid-activated antimicrobial peptide.

    Science.gov (United States)

    Li, Lina; He, Jian; Eckert, Randal; Yarbrough, Daniel; Lux, Renate; Anderson, Maxwell; Shi, Wenyuan

    2010-01-01

    Dental caries is a microbial biofilm infection in which the metabolic activities of plaque bacteria result in a dramatic pH decrease and shift the demineralization/remineralization equilibrium on the tooth surface towards demineralization. In addition to causing a net loss in tooth minerals, creation of an acidic environment favors growth of acid-enduring and acid-generating species, which causes further reduction in the plaque pH. In this study, we developed a prototype antimicrobial peptide capable of achieving high activity exclusively at low environmental pH to target bacterial species like Streptococcus mutans that produce acid and thrive under the low pH conditions detrimental for tooth integrity. The features of clavanin A, a naturally occurring peptide rich in histidine and phenylalanine residues with pH-dependent antimicrobial activity, served as a design basis for these prototype 'acid-activated peptides' (AAPs). Employing the major cariogenic species S. mutans as a model system, the two AAPs characterized in this study exhibited a striking pH-dependent antimicrobial activity, which correlated well with the calculated charge distribution. This type of peptide represents a potential new way to combat dental caries. PMID:19878192

  10. Bioproduction, Antimicrobial and Antioxidant Activities of Compounds from Chlorella vulgaris

    Directory of Open Access Journals (Sweden)

    Danielli M.M. Dantas

    2015-09-01

    Full Text Available Various crude extract preparations (ethanol, methanol, buthanol, acetone, DMSO and water from the green alga Chlorella vulgaris were examined for Antioxidant activity, Phytochemical screening and Antimicrobial properties. In vitro free radical quenching and total antioxidant activity of extracts were investigated with 1, 1-diphenyl-2- picryl hydrazyl (DPPH, and compared with cathequin and Gallic acid as positive controls. In most cases, results showed a significant association between the antioxidant potency and the total phenolics content. The aqueous extract showed both the highest antioxidant activity for inhibition scavenging (68.5% and highest phenolic content (3.45 mg/ mL. Antimicrobial activities were carried out using disc diffusion assays and the broth dilution method against Gram-positive and Gram-negative bacteria. Results demonstrated activity between the aqueous extract and most specimens (Proteus mirabilis, Klebsiella pneumoniae, Salmonella enteretidis, Bacillus subtilis and Escherichia coli. These results suggest that the aqueous crude extract of C. vulgaris could be considered as a biological antioxidant and antimicrobial agent, and a valuable tool for the biotechnology field.

  11. Antimicrobial Activity of UV-Induced Phenylamides from Rice Leaves

    Directory of Open Access Journals (Sweden)

    Hye Lin Park

    2014-11-01

    Full Text Available Rice produces a wide array of phytoalexins in response to pathogen attacks and UV-irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from UV-treated rice leaves showed that several phenolic compounds in addition to sakuranetin accumulated remarkably in rice leaves. We isolated two compounds from UV-treated rice leaves using silica gel column chromatography and preparative HPLC. The isolated phenolic compounds were identified as phenylamide compounds: N-trans-cinnamoyltryptamine and N-p-coumaroylserotonin. Expression analysis of biosynthetic genes demonstrated that genes for arylamine biosynthesis were upregulated by UV irradiation. This result suggested that phenylamide biosynthetic pathways are activated in rice leaves by UV treatment. To unravel the role of UV-induced phenylamides as phytoalexins, we examined their antimicrobial activity against rice fungal and bacterial pathogens. N-trans-Cinnamoyltryptamine inhibited the growth of rice brown spot fungus (Bipolaris oryzae. In addition to the known antifungal activity to the blast fungus, sakuranetin had antimicrobial activity toward B. oryzae and Rhizoctonia solani (rice sheath blight fungus. UV-induced phenylamides and sakuranetin also had antimicrobial activity against rice bacterial pathogens for grain rot (Burkholderia glumae, blight (Xanthomonas oryzae pv. oryzae and leaf streak (X. oryzae pv. oryzicola diseases. These findings suggested that the UV-induced phenylamides in rice are phytoalexins against a diverse array of pathogens.

  12. Effects of an intravitreal injection of interleukin-35-expressing plasmid on pro-inflammatory and anti-inflammatory cytokines

    Science.gov (United States)

    Hou, Chao; Wu, Qianni; Ouyang, Chen; Huang, Ting

    2016-01-01

    In order to explore the potential effects of interleukin (IL)-35 on IL-10, transforming growth factor-β (TGF-β), interferon-γ (INF)-γ, IL-12 and IL-17, a pcDNA3.1-IL-35 plasmid was injected into the vitreous cavity of BALB/c mice. Enzyme-linked immunosorbent assay, western blot analysis and quantitative PCR analysis were performed to confirm the successful expression of IL-35. Slit-lamp biomicroscopy, hematoxylin and eosin staining and immunofluorescence were employed to detect the status of eyes, and western blot analysis was performed to examine the expression of corneal graft rejection-related cytokines. There were no abnormalities in the eyes pre-mydriasis or post-mydriasis and no injuries to the cornea or retina following the injection of IL-35-expressing plasmid. An immunofluorescence assay detected the positive expression of IL-35 in corneal epithelial cells from IL-35-injected mice and negative staining in the control group. Further study revealed that IL-35 enhanced the expression of IL-10 and TGF-β which reached their highest levels at 1 and 2 weeks after injection, respectively (pIL-35-expressing plasmid (pIL-35-expressing plasmid in mice downregulates the expression of pro-inflammatory cytokines and upregulates the expression of anti-inflammatory cytokines. Thus, IL-35 may further be assessed as a potential target for the treatment of corneal graft rejection. PMID:27460435

  13. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques

    Science.gov (United States)

    Fredman, Gabrielle; Hellmann, Jason; Proto, Jonathan D.; Kuriakose, George; Colas, Romain A.; Dorweiler, Bernhard; Connolly, E. Sander; Solomon, Robert; Jones, David M.; Heyer, Eric J.; Spite, Matthew; Tabas, Ira

    2016-01-01

    Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr−/− mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability. PMID:27659679

  14. Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells

    Directory of Open Access Journals (Sweden)

    Bagaitkar Juhi

    2012-11-01

    Full Text Available Abstract Background The primary, stable metabolite of nicotine [(S-3-(1-methyl-2-pyrrolidinyl pyridine] in humans is cotinine [(S-1-methyl-5-(3-pyridinyl-2-pyrrolidinone]. We have previously shown that cotinine exposure induces convergence and amplification of the GSK3β-dependent PI3 kinase and cholinergic anti-inflammatory systems. The consequence is reduced pro-inflammatory cytokine secretion by human monocytes responding to bacteria or LPS, a TLR4 agonist. Findings Here we show that cotinine-induced inflammatory suppression may not be restricted to individual Toll-like receptors (TLRs. Indeed, in monocytic cells, cotinine suppresses the cytokine production that is normally resultant upon agonist-specific engagement of all of the major surface exposed TLRs (TLR 2/1; 2/6; 4 and 5, although the degree of suppression varies by TLR. Conclusions These results provide further mechanistic insight into the increased susceptibility to multiple bacterial infections known to occur in smokers. They also establish THP-1 cells as a potentially suitable model with which to study the influence of tobacco components and metabolites on TLR-initiated inflammatory events.

  15. Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease.

    Directory of Open Access Journals (Sweden)

    Kerstin Berer

    Full Text Available Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE, an animal model for Multiple sclerosis (MS. The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of TH17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred TH17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of TH17 cells in the gut was partially dependent on the gut homing receptor α4β7-mediated adhesion to the intestine. Administration of α4β7 blocking-antibodies increased the peripheral availability of TH17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.

  16. Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis - a targeted 'omics study.

    Science.gov (United States)

    Lee, Yie Hou; Cui, Liang; Fang, Jinling; Chern, Bernard Su Min; Tan, Heng Hao; Chan, Jerry K Y

    2016-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (-50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (-39%, -54% and -76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis. PMID:27193963

  17. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming

    Directory of Open Access Journals (Sweden)

    Coffey Matt

    2011-02-01

    Full Text Available Abstract Background As well as inducing direct oncolysis, reovirus treatment of melanoma is associated with activation of innate and adaptive anti-tumour immune responses. Results Here we characterise the effects of conditioned media from reovirus-infected, dying human melanoma cells (reoTCM, in the absence of live virus, to address the immune bystander potential of reovirus therapy. In addition to RANTES, IL-8, MIP-1α and MIP-1β, reovirus-infected melanoma cells secreted eotaxin, IP-10 and the type 1 interferon IFN-β. To address the mechanisms responsible for the inflammatory composition of reoTCM, we show that IL-8 and IFN-β secretion by reovirus-infected melanoma cells was associated with activation of NF-κB and decreased by pre-treatment with small molecule inhibitors of NF-κB and PKR; specific siRNA-mediated knockdown further confirmed a role for PKR. This pro-inflammatory milieu induced a chemotactic response in isolated natural killer (NK cells, dendritic cells (DC and anti-melanoma cytotoxic T cells (CTL. Following culture in reoTCM, NK cells upregulated CD69 expression and acquired greater lytic potential against tumour targets. Furthermore, melanoma cell-loaded DC cultured in reoTCM were more effective at priming adaptive anti-tumour immunity. Conclusions These data demonstrate that the PKR- and NF-κB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing can recruit and activate innate and adaptive effector cells, thus potentially altering the tumour microenvironment to support bystander immune-mediated therapy as well as direct viral oncolysis.

  18. Spectrum and activity of novel antimicrobial peptidomimetics

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line

    Antibiotics have been an effective weapon against bacterial infections for over 50 years. However, bacterial resistance towards conventional antibiotics has increased considerably within the last decades and the number of antibacterial agents available for treating complicated bacterial infections...... the activity of the peptidomimetics against a range food borne and nosocomial pathogenic bacteria. These structure-activity studies demonstrated that peptide length was important for high antibacterial activity since analogues with a length shorter than 12 residues were virtually inactive. In the present...

  19. Screening of Australian plants for antimicrobial activity against Campylobacter jejuni.

    Science.gov (United States)

    Kurekci, Cemil; Bishop-Hurley, Sharon L; Vercoe, Philip E; Durmic, Zoey; Al Jassim, Rafat A M; McSweeney, Christopher S

    2012-02-01

    Campylobacter jejuni is the most common cause of acute enteritis in humans, with symptoms such as diarrhoea, fever and abdominal cramps. In this study, 115 extracts from 109 Australian plant species were investigated for their antimicrobial activities against two C. jejuni strains using an in vitro broth microdilution assay. Among the plants tested, 107 (93%) extracts showed activity at a concentration between 32 and 1024 µg/mL against at least one C. jejuni strain. Seventeen plant extracts were selected for further testing against another six C. jejuni strains, as well as Campylobacter coli, Escherichia coli, Salmonella typhimurium, Bacillus cereus, Proteus mirabilis and Enterococcus faecalis. The extract from Eucalyptus occidentalis demonstrated the highest antimicrobial activity, with an inhibitory concentration of 32 µg/mL against C. jejuni and B. cereus. This study has shown that extracts of selected Australian plants possess antimicrobial activity against C. jejuni and thus may have application in the control of this organism in live poultry and retail poultry products.

  20. Antimicrobial and antihyperglycemic activities of Musa paradisiaca flowers

    Institute of Scientific and Technical Information of China (English)

    Sunil Jawla; Y Kumar; MSY Khan

    2012-01-01

    Objective: To screen the antimicrobial and antihyperglycemic activities of Musa paradisiaca (M. paradisiaca) flowers. Methods: The EtOH and EtOH: water (1:1) extracts of M. paradisiaca flowers were screened for antibacterial and antifungal activity against standard strains of Bacillussubtilis (K. pneumoniae), Proteus mirabilis (P. mirabilis), Pseudomonas aeruginosa (P. aeruginosa),Streptococcus pneumoniae (B. subtilis), Bacillus cereus (B. cereus), Escherichia coli (E. coli), Klebsiella pneumoniae typhimurium (S. typhimurium) and Candida albicans (C. albicans), Cryptococcus albidus (C.albidus (S. pneumoniae), Staphylococcus aureus (S. aureus), Salmonella ) against amikacin and clotrimazole respectively. Both the extracts were also administered to normal and alloxan induced diabetic rats. The blood glucose levels were measured daily after oral administration of extracts at doses of 100, 250 and 500 mg/(kg.d). Result: The EtOH and EtOH:water (1:1) extracts exhibited antimicrobial activity with minimum inhibitory concentrations ranging from 5.62-25.81 and 7.60-31.50 μg/mL respectively. Both the extracts reversed the permanent hyperglycemia within a week in alloxan induced diabetic rats. The EtOH extract (250 mg/kg) was found to be 7.69% more potent hypoglycemic effect than standard oral hypoglycemic drug, glibenclamide 0.2 mg/kg b.w., respectively. Conclusion: The alcoholic extracts of M. paradisiaca flowers showed potent antihyperglycemic and moderate antimicrobial activities.

  1. Antimicrobial activities of endophytic fungi isolated from Ophiopogon japonicus (Liliaceae

    Directory of Open Access Journals (Sweden)

    Liang Hanqiao

    2012-11-01

    Full Text Available Abstract Background Drug resistance in bacteria has become a global concern and the search for new antibacterial agents is urgent and ongoing. Endophytes provide an abundant reservoir of bioactive metabolites for medicinal exploitation, and an increasing number of novel compounds are being isolated from endophytic fungi. Ophiopogon japonicus, containing compounds with antibacterial activity, is a traditional Chinese medicinal plant used for eliminating phlegm, relieving coughs, latent heat in the lungs, and alleviating diabetes mellitus. We investigated the antimicrobial activities of 30 strains of O. japonicus. Methods Fungal endophytes were isolated from roots and stems of O. japonicus collected from Chongqing City, southwestern China. Mycelial extracts (MC and fermentation broth (FB were tested for antimicrobial activity using peptide deformylase (PDF inhibition fluorescence assays and MTT cell proliferation assays. Results A total of 30 endophytic strains were isolated from O. japonicus; 22 from roots and eight from stems. 53.33% of the mycelial extracts (MC and 33.33% of the fermentation broths (FB displayed potent inhibition of PDF. 80% of MC and 33.33% of FB significantly inhibited Staphylococcus aureus. 70% of MC and 36.67% of FB showed strong activities against Cryptococcus neoformans. None showed influence on Escherichia coli. Conclusion The secondary metabolites of endophytic fungi from O. japonicus are potential antimicrobial agents.

  2. Antimicrobial and Cytotoxic Activities of Extracts from Laurus nobilis Leaves

    KAUST Repository

    Felemban, Shaza

    2011-05-01

    The cytotoxic activity and antimicrobial properties of crude extracts from Laurus nobilis were investigated. With the use of the organic solvents, methanol and ethanol, crude extracts were obtained. To determine the availability of active bio‐compounds, an analysis using liquid chromatography was conducted. The crude extract was also tested for antimicrobial activity. The disc diffusion method was used against the bacterium Escherichia coli. The results showed a weak antimicrobial activity against E. coli. For cytotoxicity testing, the crude extract was studied on four cell-­lines: human breast adenocarcinoma, human embryonic kidney, HeLa (human cervical adenocarcinoma), and human lung fibroblast. From the alamarBlue® assay results, the extracts most potently affected the cell-­lines of human breast adenocarcinoma and human embryonic kidney. Using the lactate dehydrogenase (LDH) assay, an effect on human embryonic kidney was most prominent. With these findings, a suggestion that the crude extract of Laurus nobilis may have antiproliferative properties is put forth, with the possibility of this mechanism being induction of apoptosis with the involvement of Nuclear Factor Kappa κB (NF κB).

  3. Antimicrobial activity of Rubus chamaemorus leaves.

    Science.gov (United States)

    Thiem, B; Goślińska, O

    2004-01-01

    The antibacterial activity of Rubus chamaemorus leaf butanolic fraction of the methanol extract and ellagic acid was evaluated against some Gram-positive and Gram-negative bacteria. Antimycotic activity was assayed against Candida albicans. MICs and MBCs were determined by broth dilution test and by disc diffusion method. PMID:14693229

  4. Synthesis, antimicrobial and antioxidative activity of some new isatin derivatives

    Directory of Open Access Journals (Sweden)

    Šekularac Gavrilo M.

    2014-01-01

    Full Text Available The isatin derivatives, Schiff bases, were synthesized by the reaction of isatin and various substituted primary amines and characterized by several spectroscopic methods. Investigation of the antimicrobial activity of the synthesized compounds was performed by the agar dilution method, against different strains of bacteria and one fungi. The antioxidative activity of the synthesized compounds was also determined. Some of the compounds have shown the significant activity against the selected strains of microorganisms and the antioxidative activity. [Projekat Ministarstva nauke Republike Srbije, br. 172013 i III 46010

  5. STUDIES ON THE EFFICACY OF ALOE VERA ON ANTIMICROBIAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    T. Karpagam

    2011-04-01

    Full Text Available The aqueous, ethanolic, methanolic, petroleum ether and acetone extracts of Aloe vera were screened for anti-microbial activity using the Minimal Inhibitory Concentration (MIC method. They were tested against five bacteria (Escherischia coli, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumonia and Staphylococcus aureus. The susceptibility of the microorganisms to the extracts in different concentrations plants were compared. The active component in the extract was determined using HPLC technique. The main aim of this study was to find anti- microbial activity of Aloe vera and to find the presence of active compounds present for the treatment of disease caused by pathogenic microorganism .

  6. Early pro-inflammatory cytokine elevations in the DBA/2J mouse model of glaucoma

    OpenAIRE

    Wilson, Gina N.; Inman, Denise M.; Denger-Crish, Christine M.; Smith, Matthew A.; Crish, Samuel D.

    2015-01-01

    Background Neuroinflammation—astrogliosis, microglial activation, and changes in cytokine signaling—is a prominent feature of neurodegenerative disorders. Glaucoma is a group of chronic neurodegenerative conditions that make up the leading cause of irreversible blindness worldwide. Neuroinflammation has been postulated to play a significant role in the pathogenesis and progression of glaucomatous neurodegeneration. Though much is known regarding inflammation in the eye in glaucoma, little is ...

  7. Antimicrobial activity in vitro of plumbagin isolated from Plumbago species

    Directory of Open Access Journals (Sweden)

    Selma Ribeiro de Paiva

    2003-10-01

    Full Text Available Plumbagin is a naturally occurring naphthoquinone isolated from roots of Plumbago scandens. The plant was collected at the Campus of Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. P. scandens is used as a traditional medicine for the treatment of several diseases. The antimicrobial activity of plumbagin was evaluated using the macrodilution method. The compound exhibited relatively specific activity against bacteria and yeast. The minimum inhibitory concentration test showed the growth inhibiton of Staphylococcus aureus at a concentration of 1.56 µg/ml and of Candida albicans at a concentration of 0.78 µg/ml. These results suggest the naphthoquinone plumbagin as a promising antimicrobial agent.

  8. Antimicrobial activity and chemical investigation of Brazilian Drosera.

    Science.gov (United States)

    Ferreira, Dalva Trevisan; Andrei, César Cornélio; Saridakis, Halha Ostrensky; Faria, Terezinha de Jesus; Vinhato, Elisângela; Carvalho, Kátia Eliane; Daniel, Juliana Feijó Souza; Machado, Sílvio Luiz; Saridakis, Dennis Panayotis; Braz-Filho, Raimundo

    2004-11-01

    The antimicrobial activity of three different extracts (hexanic, ethyl acetate, methanol) obtained from Brazilian Drosera species (D. communis, D. montana var. montana, D. brevifolia, D. villosa var. graomogolensis, D. villosa var. villosa, Drosera sp. 1, and Drosera sp. 2 ) were tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecium (ATCC23212), Pseudomonas aeruginosa (ATCC27853), Escherichia coli (ATCC11229), Salmonella choleraesuis (ATCC10708), Klebsiella pneumoniae (ATCC13883), and Candida albicans (a human isolate). Better antimicrobial activity was observed with D. communis and D. montana var. montana ethyl acetate extracts. Phytochemical analyses from D. communis, D. montana var. montana and D. brevifolia yielded 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin); long chain aliphatic hydrocarbons were isolated from D. communis and from D. villosa var. villosa, a mixture of long chain aliphatic alcohols and carboxylic acids, was isolated from D. communis and 3b-O-acetylaleuritolic acid from D. villosa var. villosa. PMID:15654434

  9. Antimicrobial activity and chemical investigation of Brazilian Drosera

    Directory of Open Access Journals (Sweden)

    Dalva Trevisan Ferreira

    2004-11-01

    Full Text Available The antimicrobial activity of three different extracts (hexanic, ethyl acetate, methanol obtained from Brazilian Drosera species (D. communis, D. montana var. montana, D. brevifolia, D. villosa var. graomogolensis, D. villosa var. villosa, Drosera sp. 1, and Drosera sp. 2 were tested against Staphylococcus aureus (ATCC 25923, Enterococcus faecium (ATCC23212, Pseudomonas aeruginosa (ATCC27853, Escherichia coli (ATCC11229, Salmonella choleraesuis (ATCC10708, Klebsiella pneumoniae (ATCC13883, and Candida albicans (a human isolate. Better antimicrobial activity was observed with D. communis and D. montana var. montana ethyl acetate extracts. Phytochemical analyses from D. communis, D. montana var. montana and D. brevifolia yielded 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin; long chain aliphatic hydrocarbons were isolated from D. communis and from D. villosa var. villosa, a mixture of long chain aliphatic alcohols and carboxylic acids, was isolated from D. communis and 3b-O-acetylaleuritolic acid from D. villosa var. villosa.

  10. Antimicrobial activity of essential oils against Paenibacillus larvae

    OpenAIRE

    Gende, L. B.; Pires, Sância; Fernandez, N.J.; Damiani, M; Churio, M.S.; Fritz, R.; Eguaras, M. J.

    2012-01-01

    American foulbrood is a serious bacterial disease that affects Apis mellifera colonies; the causative agent is Paenibacillus larvae [1 ]. The aim of the study was to evaluate in vitro the antimicrobial activity of 32 essential oils against P. larvae. Oils from 21 botanical species were analyzed by gas chromatography (CG and CG/EM). All essential oils were classified according to the composition of their main components in two groups: benzene ring compounds (BRC) and terpene com...

  11. Phytochemical and Antimicrobial Activity of Digera Muricata (L.) Mart.

    OpenAIRE

    2010-01-01

    The successive Soxhlet extract of Digera muricata (L.) Mart. (Amaranthaceae) were extracted using petroleum ether, chloroform, ethanol and distilled water in ascending order of the polarity. These extracts were subjected to screening of preliminary phytochemicals tests. The results indicate the presence of alkaloids, flavonoids, phenols, tannins, terpenes and saponins. These extracts further subjected to the antimicrobial activity. Among the bacteria used, the petroleum ether extract gave hig...

  12. Design and Characterization of an Acid-Activated Antimicrobial Peptide

    OpenAIRE

    Li, Lina; He, Jian; Eckert, Randal; Yarbrough, Daniel; Lux, Renate; Anderson, Maxwell; Shi, Wenyuan

    2009-01-01

    Dental caries is a microbial biofilm infection in which the metabolic activities of plaque bacteria result in a dramatic pH decrease and shift the demineralization/ remineralization equilibrium on the tooth surface towards demineralization. In addition to causing a net loss in tooth minerals creation of an acidic environment favors growth of acid enduring and acid generating species, which causes further reduction in the plaque pH. In this study we developed a prototype antimicrobial peptide ...

  13. Antimicrobial activity and chemical investigation of Brazilian Drosera

    OpenAIRE

    Dalva Trevisan Ferreira; César Cornélio Andrei; Halha Ostrensky Saridakis; Terezinha de Jesus Faria; Elisângela Vinhato; Kátia Eliane Carvalho; Juliana Feijó de Souza Daniel; Sílvio Luiz Machado; Dennis Panayotis Saridakis; Raimundo Braz-Filho

    2004-01-01

    The antimicrobial activity of three different extracts (hexanic, ethyl acetate, methanol) obtained from Brazilian Drosera species (D. communis, D. montana var. montana, D. brevifolia, D. villosa var. graomogolensis, D. villosa var. villosa, Drosera sp. 1, and Drosera sp. 2 ) were tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecium (ATCC23212), Pseudomonas aeruginosa (ATCC27853), Escherichia coli (ATCC11229), Salmonella choleraesuis (ATCC10708), Klebsiella pneumoniae (ATCC1...

  14. Screening marine organisms for antimicrobial activity against clinical pathogens

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; Wahidullah, S.; Tonima, K.; DeSouza, L.

    extracts of forty marine organisms belonging to different phyla and fractions of active extracts were screened for their antimicrobial effects on human pathogens. A broad panel of microbial pathogens associated with various skin infections, urinary... aeruginosa B2 Gram Negative Urinary tract infection 3. Staphylococcus aureus B3 Gram Positive Skin infection 4. Salmonella typhi (i) B4 Gram Negative Typhoid 5. Shigella flexineri B5 Gram Negative Gastrointestin al infection 6. Klebsiella sp. B6 Gram...

  15. ANTIMICROBIAL ACTIVITY OF NINE MEDICINAL PLANTS FROM VERACRUZ, MEXICO

    OpenAIRE

    Chena-Becerra, F; Palmeros-Sánchez, B; Fernández, M.S; Lozada-García, J.A

    2014-01-01

    The medicinal plants are an alternative source to the treatment of primary health care problems. An ethnobotanical study performed on Tlalchy, Ixhuacán de los Reyes, Veracruz, México, allowed the selection of nine plant species involved in infectious diseases treatments. Antimicrobial activities of ethanolic crude extracts were tested on fifteen bacterial and yeast clinical isolates. Every extract showed a level of inhibition against almost all the microorganisms assayed. According to the Cli...

  16. A new active and antimicrobial package for preservation of vegetables

    OpenAIRE

    Taboada Rodríguez, Amaury

    2013-01-01

    [ENG] The food packaging industry is demanding new packages able to improve the quality of the packed products. In this regard some of the problems to be solved are the recyclable and compostable character of the materials, the antimicrobial properties of some substances to be involved in the packaging system and the optimum control of the internal atmosphere in the package. As a solution for these problems a new flow-pack active packaging design was proposed to be developed in this investiga...

  17. Synthesis and Antimicrobial Activity of Some Chalcone Derivatives

    OpenAIRE

    Prasad, Y. Rajendra; Rao, A. Lakshmana; Rambabu, R.

    2008-01-01

    In an effort to develop antimicrobial agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehydes in the presence of aqueous solution of potassium hydroxide and ethanol at room temperature. The synthesized compounds were characterized by means of their IR, 1H-NMR spectral data and elemental analysis. All the compounds were tested for their antibacterial and antifungal activities by the cup plate method.

  18. ANTIMICROBIAL ACTIVITY OF WHITE AND PINK NELUMBO NUCIFERA GAERTN FLOWERS

    OpenAIRE

    D.BRINDHA, D.ARTHI

    2013-01-01

    Nelumbo nucifera Gaertn (Family: Nelumbonaceae), medicinally versatile and used as an important raw material of age-old traditional medical practices like Ayurveda and folk medicine. Bioassays for antimicrobial activities were carried out using hydroethanolic extract of both white and pink flowers of Nelumbo nucifera Gaertn plant. Both the flower extracts were tested against five important bacterial strains and two fungal strains. Further, Minimum Inhibitory Concentration (MIC) was evaluated ...

  19. Thioredoxin ameliorates cutaneous inflammation by regulating the epithelial production and release of pro-Inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Hai eTian

    2013-09-01

    Full Text Available Human thioredoxin-1 (TRX is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-. It has been demonstrated that systemic administration and transgenic overexpression of TRX ameliorate inflammation in various animal models, but its anti-inflammatory mechanism is not well characterized. We investigated the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX in a murine irritant contact dermatitis (ICD induced by croton oil. Topically applied rhTRX was distributed only in the skin tissues under both non-inflammatory and inflammatory conditions, and significantly suppressed the inflammatory response by inhibiting the production of cytokines and chemokines, such as TNF-α, Il-1β, IL-6, CXCL-1, and MCP-1. In an in vitro study, rhTRX also significantly inhibited the formation of cytokines and chemokines produced by keratinocytes after exposure to croton oil and phorbol 12-myristate 13-acetate. These results indicate that TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. As a promising new approach, local application of TRX may be useful for the treatment of various skin and mucosal inflammatory disorders.

  20. Antimicrobial activity of bone cements embedded with organic nanoparticles

    Directory of Open Access Journals (Sweden)

    Perni S

    2015-10-01

    Full Text Available Stefano Perni,1,2 Victorien Thenault,1 Pauline Abdo,1 Katrin Margulis,3 Shlomo Magdassi,3 Polina Prokopovich1,2 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 2Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; 3Casali Institute, Institute of Chemistry, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem, IsraelAbstract: Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate [PMMA], hydroxyapatite, and brushite and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, and Acinetobacter baumannii. Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No ­detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial

  1. Screening antimicrobial activity of various extracts of Urtica dioica.

    Science.gov (United States)

    Modarresi-Chahardehi, Amir; Ibrahim, Darah; Fariza-Sulaiman, Shaida; Mousavi, Leila

    2012-12-01

    Urtica dioica or stinging nettle is traditionally used as an herbal medicine in Western Asia. The current study represents the investigation of antimicrobial activity of U. dioica from nine crude extracts that were prepared using different organic solvents, obtained from two extraction methods: the Soxhlet extractor (Method I), which included the use of four solvents with ethyl acetate and hexane, or the sequential partitions (Method II) with a five solvent system (butanol). The antibacterial and antifungal activities of crude extracts were tested against 28 bacteria, three yeast strains and seven fungal isolates by the disc diffusion and broth dilution methods. Amoxicillin was used as positive control for bacteria strains, vancomycin for Streptococcus sp., miconazole nitrate (30 microg/mL) as positive control for fungi and yeast, and pure methanol (v/v) as negative control. The disc diffusion assay was used to determine the sensitivity of the samples, whilst the broth dilution method was used for the determination of the minimal inhibition concentration (MIC). The ethyl acetate and hexane extract from extraction method I (EA I and HE I) exhibited highest inhibition against some pathogenic bacteria such as Bacillus cereus, MRSA and Vibrio parahaemolyticus. A selection of extracts that showed some activity was further tested for the MIC and minimal bactericidal concentrations (MBC). MIC values of Bacillus subtilis and Methicillin-resistant Staphylococcus aureus (MRSA) using butanol extract of extraction method II (BE II) were 8.33 and 16.33mg/mL, respectively; while the MIC value using ethyl acetate extract of extraction method II (EAE II) for Vibrio parahaemolyticus was 0.13mg/mL. Our study showed that 47.06% of extracts inhibited Gram-negative (8 out of 17), and 63.63% of extracts also inhibited Gram-positive bacteria (7 out of 11); besides, statistically the frequency of antimicrobial activity was 13.45% (35 out of 342) which in this among 21.71% belongs to

  2. Antimicrobial activity of silver/starch/polyacrylamide nanocomposite.

    Science.gov (United States)

    Abdel-Halim, E S; Al-Deyab, Salem S

    2014-07-01

    A novel silver/starch/polyacrylamide nanocomposite hydrogel was prepared by grafting acrylamide onto starch in presence of silver nitrate by use of ammonium persulphate as an initiator and N,N-methylene-bisacrylamide as a crosslinking agent, then reducing the silver ions enclosed in the hydrogel structure to silver nanoparticles by treating the hydrogel with sodium hydroxide solution. All factors which affect the grafting/crosslinking reaction were optimized and the concentration of silver ion was changed from 0ppm to 50ppm. The produced nanocomposite hydrogel was characterized for its nanosilver content and the UV-spectra showed similar absorption spectra at wavelength 405nm for all AgNO3 concentrations but the plasmon showed increase in the intensity of the absorption peak as AgNO3 concentration incorporated to the hydrogel structure increases. The nanocomposite hydrogel was also characterized for its antimicrobial activity toward two types of bacteria and two types of fungi. The results showed that the hydrogel with 0ppm silver content has no antimicrobial activity, and that the antimicrobial activity expressed as inhibition zone increases as the silver content increases from 5ppm to 50ppm.

  3. Biocompatible cellulose-based superabsorbent hydrogels with antimicrobial activity.

    Science.gov (United States)

    Peng, Na; Wang, Yanfeng; Ye, Qifa; Liang, Lei; An, Yuxing; Li, Qiwei; Chang, Chunyu

    2016-02-10

    Current superabsorbent hydrogels commercially applied in the disposable diapers have disadvantages such as weak mechanical strength, poor biocompatibility, and lack of antimicrobial activity, which may induce skin allergy of body. To overcome these hassles, we have developed novel cellulose based hydrogels via simple chemical cross-linking of quaternized cellulose (QC) and native cellulose in NaOH/urea aqueous solution. The prepared hydrogel showed superabsorbent property, high mechanical strength, good biocompatibility, and excellent antimicrobial efficacy against Saccharomyces cerevisiae. The presence of QC in the hydrogel networks not only improved their swelling ratio via electrostatic repulsion of quaternary ammonium groups, but also endowed their antimicrobial activity by attraction of sections of anionic microbial membrane into internal pores of poly cationic hydrogel leading to the disruption of microbial membrane. Moreover, the swelling properties, mechanical strength, and antibacterial activity of hydrogels strongly depended on the contents of quaternary ammonium groups in hydrogel networks. The obtained data encouraged the use of these hydrogels for hygienic application such as disposable diapers.

  4. Determination of Yeasts Antimicrobial Activity in Milk and Meat Products

    Directory of Open Access Journals (Sweden)

    L.B. Roostita

    2011-12-01

    Full Text Available The research was arranged to isolate yeasts from livestock products and then the yeasts antimicrobial activity was tested towards putrefaction and pathogenic bacteria. Yeasts isolated from livestock products using Malt Extract Agar (MEA, the total yeasts population counted with using total plate count method, antimicrobial activity tested using diffusion methods against Pseudomonas aerugenes, Staphylococcus aureus and Escherichia coli and then the chosen isolate identified with using 18s RNA method. The results have shown that the total yeasts population on pasteurized cow’s milk were 1.2×106 cfu/g, fruit yoghurt 5.4×106 cfu/g, lamb meat 1×105 cfu/g, beef 1×105 cfu/g and beef sausages 1×106 cfu/g total yeasts population. Fruit yoghurt isolate shown the best antimicrobial activity with 35 mm clear zone diameter against Pseudomonas aerugenes, 8 mm clear zone diameter against Staphylococcus aureus and 10 mm clear zone diameter against Escherichia coli. The 18 s RNA test shown that fruit yoghurt isolate was 100% (FR3-F primer and 99% (FR3-R primer identical with Candida parapsilosis.

  5. Acupuncture Induces a Pro-Inflammatory Immune Response Intensified by a Conditioning-Expectation Effect

    DEFF Research Database (Denmark)

    Karst, M; Schneidewind, D; Schneinichen, D;

    2010-01-01

    BACKGROUND: In a previous study it has been shown that acupuncture activates the respiratory burst (RB) of neutrophils as measured by the differences to baseline of the mean channel number of fluorescence intensity (mfi) in volunteers. Since this result could have been affected by a placebo effect......, a study has been designed that controls for the different facets of placebo mechanisms such as expectancy, suggestibility, and conditioning. PARTICIPANTS AND METHODS: 60 healthy volunteers were randomized either to acupuncture of the acupoint Large Intestine 11 (LI 11) (groups 1 and 2) or relaxation...... (group 3) twice a week for 4 weeks. Only acupuncture group 1 and the relaxation group were provided with the additional suggestion that the treatment may strengthen the immune system. RESULTS: The repeated measurement analysis for differences of follow-ups to baseline showed significantly different...

  6. Acupuncture induces a pro-inflammatory immune response intensified by a conditioning-expectation effect

    DEFF Research Database (Denmark)

    Karst, M.; Schneidewind, D.; Scheinchen, D.;

    2010-01-01

    BACKGROUND: In a previous study it has been shown that acupuncture activates the respiratory burst (RB) of neutrophils as measured by the differences to baseline of the mean channel number of fluorescence intensity (mfi) in volunteers. Since this result could have been affected by a placebo effect......, a study has been designed that controls for the different facets of placebo mechanisms such as expectancy, suggestibility, and conditioning. PARTICIPANTS AND METHODS: 60 healthy volunteers were randomized either to acupuncture of the acupoint Large Intestine 11 (LI 11) (groups 1 and 2) or relaxation...... (group 3) twice a week for 4 weeks. Only acupuncture group 1 and the relaxation group were provided with the additional suggestion that the treatment may strengthen the immune system. RESULTS: The repeated measurement analysis for differences of follow-ups to baseline showed significantly different...

  7. Consecutive Low Doses of Cyclosporine A Induce Pro-Inflammatory Cytokines and Accelerate Allograft Skin Rejection

    Directory of Open Access Journals (Sweden)

    Luis I. Terrazas

    2011-05-01

    Full Text Available Cyclosporine A (CsA is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of CsA used. To test the hypothesis that minimal doses of CsA may show different outcomes on grafts, we used an experimental model for skin transplants in mice. ICR outbred mice received skin allografts and were either treated daily with different doses of CsA or left untreated. Untreated mice showed allograft rejection within 14 days, with graft necrosis, infiltration of neutrophils and macrophages and displayed high percentages of CD8+ T cells in the spleens, which were associated with high serum levels of IL-12, IFN-g and TNF-α. As expected, mice treated with therapeutic doses of CsA (15 mg/kg did not show allograft rejection within the follow-up period of 30 days and displayed the lowest levels of IL-12, IFN-g and TNF-α as well as a reduction in CD8+ lymphocytes. In contrast, mice treated with consecutive minimal doses of CsA (5 × 10−55 mg/kg displayed an acute graft rejection as early as one to five days after skin allograft; they also displayed necrosis and strong inflammatory infiltration that was associated with high levels of IL-12, IFN-g and TNF-α. Moreover, the CD4+ CD25hiFoxP3+ subpopulation of cells in the spleens of these mice was significantly inhibited compared with animals that received the therapeutic treatment of CsA and those treated with placebo. Our data suggest that consecutive, minimal doses of CsA may affect Treg cells and may stimulate innate immunity.

  8. Aedesin: structure and antimicrobial activity against multidrug resistant bacterial strains.

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    Sylvain Godreuil

    Full Text Available Multidrug resistance, which is acquired by both Gram-positive and Gram-negative bacteria, causes infections that are associated with significant morbidity and mortality in many clinical settings around the world. Because of the rapidly increasing incidence of pathogens that have become resistant to all or nearly all available antibiotics, there is a need for a new generation of antimicrobials with a broad therapeutic range for specific applications against infections. Aedesin is a cecropin-like anti-microbial peptide that was recently isolated from dengue virus-infected salivary glands of the Aedes aegypti mosquito. In the present study, we have refined the analysis of its structural characteristics and have determined its antimicrobial effects against a large panel of multidrug resistant bacterial strains, directly isolated from infected patients. Based the results from nuclear magnetic resonance spectroscopy analysis, Aedesin has a helix-bend-helix structure typical for a member of the family of α-helix anti-microbial peptides. Aedesin efficiently killed Gram-negative bacterial strains that display the most worrisome resistance mechanisms encountered in the clinic, including resistance to carbapenems, aminoglycosides, cephalosporins, 4th generation fluoroquinolones, folate inhibitors and monobactams. In contrast, Gram-positive strains were insensitive to the lytic effects of the peptide. The anti-bacterial activity of Aedesin was found to be salt-resistant, indicating that it is active under physiological conditions encountered in body fluids characterized by ionic salt concentrations. In conclusion, because of its strong lytic activity against multidrug resistant Gram-negative bacterial strains displaying all types of clinically relevant resistance mechanisms known today, Aedesin might be an interesting candidate for the development of alternative treatment for infections caused by these types of bacteria.

  9. Pro-inflammatory cytokines and psychotherapy in depression: Results from a randomized clinical trial.

    Science.gov (United States)

    Del Grande da Silva, Giovanna; Wiener, Carolina David; Barbosa, Luana Porto; Gonçalves Araujo, Jaciana Marlova; Molina, Mariane Lopez; San Martin, Pedro; Oses, Jean Pierre; Jansen, Karen; Dias de Mattos Souza, Luciano; Azevedo da Silva, Ricardo

    2016-04-01

    Depression is a serious condition that is associated with great psychic suffering and major impairments on the patient's general health, quality of life, and social and occupational activities. In some cases, it may lead to suicide. Regardless of the innumerous research works that have already addressed depression in wide and specific facets, there is still a lot to grasp in order to effectively help preventing and treating depression. This work presents data from a randomized clinical trial that sought to evaluate the effectiveness of two brief psychotherapeutic for Depression: Cognitive Behavioral Therapy (CBT) and Supportive-Expressive Dynamic Psychotherapy (SEDP). This was a convenience sample composed of 46 individuals that were evaluated using a structured diagnostic interview and then randomly allocated to the SEDP group. We examined baseline and post-intervention serum levels of the Interleukin-6 (IL-6) and the Tumor Necrosis Factor (TNF-α) in addition to the severity of depressive symptoms according to the Outcome Questionnaire - 45.2 (OQ-45.2) and the Beck Depression Inventory (BDI). Results show that serum IL-6 and TNF-α levels, as well as the scores from the OQ-45.2 and the BDI significantly decreased after 16 sessions of SEDP (p brief psychodynamic psychotherapy in the reduction of depressive symptoms and serum inflammatory levels that are associated with depression. PMID:26802811

  10. Antimicrobial activity of some isatin-3--thiosemicarbazone complexes

    OpenAIRE

    SANDRA S. KONSTANTINOVIC; Radovanovic, Blaga C.; Sovilj, Sofija P.; SVETLANA STANOJEVIC

    2008-01-01

    Isatin-3-thiosemicarbazone complexes with Co(II), Ni(II), Cu(II), Zn(II), Hg(II) and Pd(II) were synthesized and evaluated for their antimicrobial activity against 7 pathogenic bacteria and 4 fungi. The complexes have an enhanced activity compared to the ligand due to transition metal involved in coordination. The anti-amoebic activity in vitro was evaluated against the HM1:IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The preliminar...

  11. Low-level laser therapy modulates pro-inflammatory cytokines after partial tenotomy.

    Science.gov (United States)

    Da Ré Guerra, Flávia; Vieira, Cristiano Pedrozo; Oliveira, Letícia Prado; Marques, Petrus Pires; Dos Santos Almeida, Marcos; Pimentel, Edson Rosa

    2016-05-01

    Tendon injuries give rise to substantial morbidity, and current understanding of the mechanisms involved in tendon injury and repair is limited. This lesion remains a clinical issue because the injury site becomes a region with a high incidence of recurrent rupture and has drawn the attention of researchers. We already demonstrated that low-level laser therapy (LLLT) stimulates the synthesis and organization of collagen I, MMP-9, and MMP-2 and improved the gait recovery of the treated animals. The aim of this study was to evaluate the effects of LLLT in the nitric oxide and cytokines profile during the inflammatory and remodeling phases. Adult male rats were divided into the following groups: G1-intact, G2- injured, G3-injured + LLLT (4 J/cm(2) continuous), G4-injured + LLLT (4 J/cm(2)-20 Hz-pulsed laser). According to the analysis, the animals were euthanized on different dates (1, 4, 8, or 15 days after injury). ELISA assay of TNF-α, IL-1β, IL-10, and TGF-β was performed. Western blotting of isoform of nitric oxide synthase (i-NOS) and nitric oxide dosage experiments was conducted. Our results showed that the pulsed LLLT seems to exert an anti-inflammatory effect over injured tendons, with reduction of the release of proinflammatory cytokines, such as TNF-α and the decrease in the i-NOS activity. Thanks to the pain reduction and the facilitation of movement, there was a stimulation in the TGF-β and IL-1β release. In conclusion, we believe that pulsed LLLT worked effectively as a therapy to reestablish the tendon integrity after rupture. PMID:26984348

  12. Flagella from five Cronobacter species induce pro-inflammatory cytokines in macrophage derivatives from human monocytes.

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    Ariadnna Cruz-Córdova

    Full Text Available Cronobacter spp. are opportunistic pathogens linked to lie-threatening infections in neonates and contaminated powdered infant formula that has been epidemiologically associated with these cases. Clinical symptoms of Cronobacter include necrotizing enterocolitis, bacteremia, and meningitis. Flagella from C. sakazakii are involved in biofilm formation and its adhesion to epithelial cells. We investigated the role of flagella from C. sakazakii ST1 and ST4, C. malonaticus, C. muytjensii, C. turicensis and C. dublinensis during the activation of cytokines (IL-8, TNF-α, and IL-10 in macrophage derivatives from human monocytes, which has not been extensively studied. The production and identity of flagella from the five Cronobacter species were visualized and recognized with anti-flagella antibodies by immunogold labeling through transmission electron microscopy. Purified flagella were dissociated into monomers in 12% SDS-PAGE Coomassie blue-stained gels showing a band of ∼28 kDa and, in addition, mass spectrometry revealed the presence of several peptides that correspond to flagellin. Flagella (100 ng induced the release of IL-8 (3314-6025 pg/ml, TNF-α (39-359 pg/ml, and IL-10 (2-96 pg/ml, in macrophage isolates from human monocytes and similar results were obtained when flagella were dissociated into monomers. Inhibition assays using three dilutions of anti-flagella antibodies (1∶10, 1∶100, and 1∶200 suppressed the secretion of IL-8, TNF-α, and IL-10 between 95-100% using 100 ng of protein. A transfection assay using 293-hTLR5 cells showed IL-8 release of 197 pg/ml and suppression in the secretion of IL-8 when anti-hTLR5-IgA antibodies were used at different concentrations. These observations suggest that flagella and flagellin are involved in an inflammatory response dependent on TLR5 recognition, which could contribute to the pathogenesis of the bacteria.

  13. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

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    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  14. Development of post-pericardiotomy syndrome is preceded by an increase in pro-inflammatory and a decrease in anti-inflammatory serological markers

    OpenAIRE

    Snefjellå Nora; Lappegård Knut

    2012-01-01

    Abstract The post-pericardiotomy syndrome (PPS) is a common complication after cardiac surgery, occuring in 10-40% of patients. PPS may prolong hospitalization, and even serious complications like tamponade and constrictive pericarditis may occur. Early diagnosis and treatment may reduce morbidity. In 50 patients transferred to our hospital after cardiac surgery we found an increase in pro-inflammatory and a decrease in anti-inflammatory cytokines at admission in the patients later developing...

  15. Using the One-Lung Method to Link p38 to Pro-Inflammatory Gene Expression during Overventilation in C57BL/6 and BALB/c Mice

    OpenAIRE

    Siegl, Stephanie; Uhlig, Stefan

    2012-01-01

    Introduction The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory signaling events ...

  16. ANTIMICROBIAL ACTIVITY OF CASSIA FISTULA LINN. LEGUMES

    OpenAIRE

    Chauhan Neelam; Bairwa Ranjan; Sharma Komal; Chauhan Nootan

    2011-01-01

    Cassia fistula Linn. (Leguminoseae), commonly known as the Golden Shower, Indian Laburnum. Cassia fistula trees as leguminous plants are popularly grown in Thailand. It is native to India, the Amazon and Sri Lanka and diffused in various countries including Mexico, China, Mauritius, South Africa, East Africa, and West Indies. The antibacterial activities of the petroleum ether, chloroform, ethyle acetate, methanolic and 50% (v/v) hydro alcoholic successive extracts of Cassia fistula (L) fruit...

  17. Antimicrobial activity of nerolidol and its derivatives against airborne microbes and further biological activities.

    Science.gov (United States)

    Krist, Sabine; Banovac, Daniel; Tabanca, Nurhayat; Wedge, David E; Gochev, Velizar K; Wanner, Jürgen; Schmidt, Erich; Jirovetz, Leopold

    2015-01-01

    Nerolidol and its derivatives, namely cis-nerolidol, O-methyl-nerolidol, O-ethyl-nerolidol, (-)-α-bisabolol, trans,trans-farnesol and its main natural source cabreuva essential oil, were tested for their antimicrobial activity against airborne microbes and antifungal properties against plant pathogens. Among the tested compounds, α-bisabolol was the most effective antimicrobial agent and trans,trans-farnesol showed the best antifungal activity. PMID:25920237

  18. Multilayer hydrogel coatings to combine hemocompatibility and antimicrobial activity.

    Science.gov (United States)

    Fischer, Marion; Vahdatzadeh, Maryam; Konradi, Rupert; Friedrichs, Jens; Maitz, Manfred F; Freudenberg, Uwe; Werner, Carsten

    2015-07-01

    While silver-loaded catheters are widely used to prevent early-onset catheter-related infections [1], long term antimicrobial protection of indwelling catheters remains to be achieved [2] and antiseptic functionalization of coatings often impairs their hemocompatibility characteristics. Therefore, this work aimed to capitalize on the antimicrobial properties of silver nanoparticles, incorporated in anticoagulant poly(ethylene glycol) (PEG)-heparin hydrogel coatings [3] on thermoplastic polyurethane materials. For prolonged antimicrobial activity, the silver-containing starPEG-heparin hydrogel layers were shielded with silver-free hydrogel layers of otherwise similar composition. The resulting multi-layered gel coatings showed long term antiseptic efficacy against Escherichia coli and Staphylococcus epidermidis strains in vitro, and similarly performed well when incubated with freshly drawn human whole blood with respect to hemolysis, platelet activation and plasmatic coagulation. The introduced hydrogel multilayer system thus offers a promising combination of hemocompatibility and long-term antiseptic capacity to meet an important clinical need.

  19. Synthesis, Characterization, and Antimicrobial Activity of Copper Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Maqusood Ahamed

    2014-01-01

    Full Text Available We studied the structural and antimicrobial properties of copper oxide nanoparticles (CuO NPs synthesized by a very simple precipitation technique. Copper (II acetate was used as a precursor and sodium hydroxide as a reducing agent. X-ray diffraction patter (XRD pattern showed the crystalline nature of CuO NPs. Field emission scanning electron microscope (FESEM and field emission transmission electron microscope (FETEM demonstrated the morphology of CuO NPs. The average diameter of CuO NPs calculated by TEM and XRD was around 23 nm. Energy dispersive X-ray spectroscopy (EDS spectrum and XRD pattern suggested that prepared CuO NPs were highly pure. CuO NPs showed excellent antimicrobial activity against various bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterococcus faecalis, Shigella flexneri, Salmonella typhimurium, Proteus vulgaris, and Staphylococcus aureus. Moreover, E. coli and E. faecalis exhibited the highest sensitivity to CuO NPs while K. pneumonia was the least sensitive. Possible mechanisms of antimicrobial activity of CuO NPs should be further investigated.

  20. Chemical properties and antioxidant and antimicrobial activities of Slovenian propolis.

    Science.gov (United States)

    Mavri, Ana; Abramovič, Helena; Polak, Tomaž; Bertoncelj, Jasna; Jamnik, Polona; Smole Možina, Sonja; Jeršek, Barbara

    2012-08-01

    The chemical composition as well as the antioxidant and antimicrobial activities of two EtOH extracts of propolis (PEEs) from Slovenia were determined. EtOH was used as extracting solvent at 70 and 96%, providing the extracts PEE70 and PEE96, respectively. The extraction with 70% EtOH was more efficient than that with 96% EtOH, as the PEE70 was richer in total phenolic compounds than the PEE96. The Slovenian propolis was characterized by different phenolic acids and flavonoids. The PEE96 was slightly richer in three specific compounds, i.e., caffeic acid, ferulic acid, and luteolin, while all other substances detected showed higher contents in the PEE70. The PEE70 showed a stronger reducing power and ability to scavenge free radicals and metal ions than the PEE96. Both PEEs were in the main more effective against Gram-positive bacteria than against fungi and Gram-negative bacteria like Salmonella and Escherichia coli, with the exception of Campylobacter. The PEE96 decreased the intracellular oxidation in Saccharomyces cerevisiae in a dose-dependent manner. The antimicrobial activities and antioxidant properties were related to the total phenolic contents. The two PEEs have the potential for use as natural antimicrobial and antioxidant additives in foods.

  1. Synthesis and Antimicrobial Activity of a Silver-Hydroxyapatite Nanocomposite

    Directory of Open Access Journals (Sweden)

    Marcos Díaz

    2009-01-01

    Full Text Available A silver-hydroxyapatite nanocomposite has been obtained by a colloidal chemical route and subsequent reduction process in H2/Ar atmosphere at 350∘C. This material has been characterized by TEM, XRD, and UV-Visible spectroscopy, showing the silver nanoparticles (∼65 nm supported onto the HA particles (∼130 nm surface without a high degree of agglomeration. The bactericidal effect against common Gram-positive and Gram-negative bacteria has been also investigated. The results indicated a high antimicrobial activity for Staphylococcus aureus, Pneumococcus and Escherichia coli, so this material can be a promising antimicrobial biomaterial for implant and reconstructive surgery applications.

  2. ANTIMICROBIAL ACTIVITY OF CLEMATIS BRACHIATA THUNB LEAF EXTRACTS

    Directory of Open Access Journals (Sweden)

    M. Mostafa* and A.J. Afolayan

    2013-01-01

    Full Text Available The antimicrobial activity as well as phytochemical screening of the hexane, acetone, methanol and water extracts of Clematis brachiata Thunb (Ranunculaceae leaves was investigated. The agar dilution assay method was used for the evaluation of the antimicrobial activity of extracts against 10 bacteria and four fungal species. The phytochemical screenings were performed by using the standard procedures. The acetone and methanol extracts were active against the 10 bacteria strains with MIC ranging between 1.0 and 3.0 mg/ml, whereas the water extract was only active against two Gram-negative bacterial strains at 10.0 mg/ml. There was no activity from the hexane extract. While there was complete growth inhibition by the acetone and methanol extracts against all the fungal species at 10 mg/ml, the hexane extract was active against all the fungal species except Candida albicans at 10 mg/ml. In contrast, the water extract did not show any activity against the fungal species. Phytochemical screening revealed the presence of phenols, tannin, saponin, flavonoids, terpenoids and glycosidic compounds and could be responsible for the above activities of the extracts. The results of this study support the traditional uses of this plant as antibiotics.

  3. Gram-positive antimicrobial activity of amino acid-based hydrogels.

    Science.gov (United States)

    Irwansyah, I; Li, Yong-Qiang; Shi, Wenxiong; Qi, Dianpeng; Leow, Wan Ru; Tang, Mark B Y; Li, Shuzhou; Chen, Xiaodong

    2015-01-27

    Antimicrobial hydrogels are prepared based on the co-assembly of commercial Fmoc-phenylalanine and Fmoc-leucine, which act as the hydrogelator and antimicrobial building block, respectively. This co-assembled antimicrobial hydrogel is demonstrated to exhibit selective bactericidal activity for gram-positive bacteria while being biocompatible with normal mammalian cells, showing great potential as an antimicrobial coating for clinical anti-infective applications.

  4. Synergistic Antimicrobial Activity of Camellia sinensis and Juglans regia against Multidrug-Resistant Bacteria

    OpenAIRE

    Amber Farooqui; Adnan Khan; Ilaria Borghetto; Kazmi, Shahana U.; Salvatore Rubino; Bianca Paglietti

    2015-01-01

    Synergistic combinations of antimicrobial agents with different mechanisms of action have been introduced as more successful strategies to combat infections involving multidrug resistant (MDR) bacteria. In this study, we investigated synergistic antimicrobial activity of Camellia sinensis and Juglans regia which are commonly used plants with different antimicrobial agents. Antimicrobial susceptibility of 350 Gram-positive and Gram-negative strains belonging to 10 different bacterial species, ...

  5. Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and pro-inflammatory markers in diet-induced obesity mice

    Science.gov (United States)

    Kim, Bohkyung; Lee, Sang Gil; Park, Young-Ki; Ku, Chai Siah; Pham, Tho X.; Wegner, Casey J.; Yang, Yue; Koo, Sung I.; Chun, Ock K.

    2016-01-01

    BACKGROUND/OBJECTIVES Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.

  6. THE EFFECT OF TAPERING PERIOD ON PLASMA PRO-INFLAMMATORY CYTOKINE LEVELS AND PERFORMANCE IN ELITE MALE CYCLISTS

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    Peter M. Tiidus

    2009-12-01

    Full Text Available The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 (IL-6, interleukin (IL-1β and tumor necrosis factor-? (TNF-α and performance in elite male cyclists. To this end, after completing 8 weeks progressive endurance exercise, twenty four high-level endurance cyclists were randomly assigned to one of two groups: a control group of cyclists (n = 12 continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists (n = 12 proceeded with a 50% reduction in weekly training volume relative to the control group. A simulated 40 min time trial (40TT performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol. Blood samples were collected immediately post-40TT from all participants at the beginning of week 1, and the end of weeks 4, 8, 9 and 11. IL-1β, IL-6 and TNFα were assayed using a standard commercial ELISA kits (Quantikine; R & D Systems, Minneapolis, MN. The mean time to complete the 40TT in the taper group decreased significantly (p < 0.01 after both 1 and 3 weeks with reduced training volume relative to the control group. There were significant reductions in (p < 0.001 IL-1β, IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period, but not at the end of the 1 week tapering period. These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen

  7. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin.

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    Michael A Bachman

    2009-10-01

    Full Text Available Nasal colonization by both gram-positive and gram-negative pathogens induces expression of the innate immune protein lipocalin 2 (Lcn2. Lcn2 binds and sequesters the iron-scavenging siderophore enterobactin (Ent, preventing bacterial iron acquisition. In addition, Lcn2 bound to Ent induces release of IL-8 from cultured respiratory cells. As a countermeasure, pathogens of the Enterobacteriaceae family such as Klebsiella pneumoniae produce additional siderophores such as yersiniabactin (Ybt and contain the iroA locus encoding an Ent glycosylase that prevents Lcn2 binding. Whereas the ability of Lcn2 to sequester iron is well described, the ability of Lcn2 to induce inflammation during infection is unknown. To study each potential effect of Lcn2 on colonization, we exploited K. pneumoniae mutants that are predicted to be susceptible to Lcn2-mediated iron sequestration (iroA ybtS mutant or inflammation (iroA mutant, or to not interact with Lcn2 (entB mutant. During murine nasal colonization, the iroA ybtS double mutant was inhibited in an Lcn2-dependent manner, indicating that the iroA locus protects against Lcn2-mediated growth inhibition. Since the iroA single mutant was not inhibited, production of Ybt circumvents the iron sequestration effect of Lcn2 binding to Ent. However, colonization with the iroA mutant induced an increased influx of neutrophils compared to the entB mutant. This enhanced neutrophil response to Ent-producing K. pneumoniae was Lcn2-dependent. These findings suggest that Lcn2 has both pro-inflammatory and iron-sequestering effects along the respiratory mucosa in response to bacterial Ent. Therefore, Lcn2 may represent a novel mechanism of sensing microbial metabolism to modulate the host response appropriately.

  8. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs

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    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V.; Negi, Narender Singh; Dubey, Uma S.; Nakhasi, Hira L.; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  9. Phenotypic switch in blood: effects of pro-inflammatory cytokines on breast cancer cell aggregation and adhesion.

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    Yue Geng

    Full Text Available Hematogeneous metastasis can occur via a cascade of circulating tumor cell adhesion events to the endothelial lining of the vasculature, i.e. the metastatic cascade. Interestingly, the pro-inflammatory cytokines IL-6 and TNF-α, which play an important role in potentiating the inflammatory cascade, are significantly elevated in metastatic breast cancer (BCa patients. Despite their high metastatic potential, human breast carcinoma cells MDA-MB-231 lack interactions with E-selectin functionalized surfaces under physiological shear stresses. We hypothesized that human plasma, 3-D tumor spheroid culture, and cytokine-supplemented culture media could induce a phenotypic switch that allows BCa cells to interact with E-selectin coated surfaces under physiological flow. Flow cytometry, immunofluorescence imaging, and flow-based cell adhesion assay were utilized to investigate the phenotypic changes of MDA-MB-231 cells with various treatments. Our results indicate that plasma, IL-6, and TNF-α promote breast cancer cell growth as aggregates and induce adhesive recruitment of BCa cells on E-selectin coated surfaces under flow. 3-D tumor spheroid culture exhibits the most significant increases in the interactions between BCa and E-selectin coated surfaces by upregulating CD44V4 and sLe(x expression. Furthermore, we show that IL-6 and TNF-α concentrations in blood may regulate the recruitment of BCa cells to the inflamed endothelium. Finally, we propose a mechanism that could explain the invasiveness of 'triple-negative' breast cancer cell line MDA-MB-231 via a positive feedback loop of IL-6 secretion and maintenance. Taken together, our results suggest that therapeutic approaches targeting cytokine receptors and adhesion molecules on cancer cells may potentially reduce metastatic load and improve current cancer treatments.

  10. Antidiarrhoeal and antimicrobial activity of Calpurnia aurea leaf extract

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    Umer Shemsu

    2013-01-01

    Full Text Available Abstract Background In Ethiopia, Calpurnia aurea is used for the treatment of syphilis, malaria, rabies, diabetes, hypertension, diarrhoea, leishmaniasis, trachoma, elephantiasis, fungal diseases and different swellings. However, despite its traditional usage as an antidiarrhoeal and antimicrobial agent, there is limited or no information regarding its effectiveness and mode of action in diarrhoea which may be caused by Shigella flexneri, Staphylococcus aureus, Escherichia coli and Salmonella typhi. Hence, we evaluated the 80% methanol (MeOH extract of dried and powdered leaves of C. aurea for its antidiarrhoeal and antimicrobial activities. Methods Swiss albino mice of either sex were divided into five groups (five/group: Group I served as control and received vehicle (1% Tween 80 at a dose of 10 ml/kg orally; Group II served as standard and received loperamide at the dose of 3 mg/kg orally; Groups III, IV and V served as test groups and received the 80% MeOH leaf extract of C. aurea at doses of 100, 200 and 400 mg/kg orally, respectively. Diarrhoea was induced by oral administration of 0.5 ml castor oil to each mouse, 1 h after the above treatments. During an observation period of 4 h, time of onset of diarrhea, total number of faecal output (frequency of defecation and weight of faeces excreted by the animals were recorded. Data were analyzed using one way analysis of variance followed by Tukey post test. Antimicrobial activity test was conducted using agar well diffusion assay. Clinical isolates tested were Salmonella typhi, Salmonella paratyphi, Salmonella typhimurium, Shigella species, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Results In castor oil induced diarrhea model, the 80% methanol leaf extract of C. aurea at 100, 200 and 400 mg/kg and the standard drug loperamide (3 mg/kg significantly reduced the time of onset of diarrhea, the frequency of defecation (total number of faecal output and weight of faeces. C

  11. The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized

    Science.gov (United States)

    Campos, Matias D.; Zucchi, Paola C.; Phung, Ann; Leonard, Steven N.; Hirsch, Elizabeth B.

    2016-01-01

    Background Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. Aim We compared the efficacy of multiple testing protocols against several “antimicrobial” film surfaces. Methods Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a “dried droplet”, and a “transfer” method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. Results Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. Conclusions Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed. PMID

  12. Antimicrobial activity and identification of potential antimicrobial compounds from aquatic pteridophyte, Azolla microphylla Kaulf.

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    Abraham, G; Yadav, R K; Kaushik, G K

    2015-04-01

    Azolla microphylla Kaulf. is an aquatic nitrogen fixing pteridophyte commonly found in aquatic habitats including paddy fields. Methanolic extract of the fronds of A. microphylla was subjected to partial purification by solvent partitioning with diethyl ether and ethyl acetate followed by hydrolysis, and further partitioning with ethyl acetate. The two fractions, thus obtained were tested for antibacterial activity. It was observed that the ethyl acetate fraction inhibited the growth of the pathogenic bacterium Xanthomonas oryzae. The GC-MS analysis of the ethyl acetate fraction showed several prominent peaks with retention time ranging from 8.83 to 45.54 min. A comparison of these peaks with the GC-MS libraries revealed that it could be eicosenes and heptadecanes with potential of antimicrobial activity. PMID:26011985

  13. Purification Technology and Antimicrobial Activity Analysis of Antimicrobial Peptide from Ovotransferrin

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tie-hua; ZHENG Jian; YE Hai-qing; YU Ya-li; ZHAO Ping; LIU Jing-bo

    2011-01-01

    Antibacterial peptides mixture purified from Ovotransferrin by pepsin digest was used as the raw material.Peptide sections with good antibacterial activity were determined after bacteriostasis experiments, its molecular weight and amino acid composition were analyzed. The results of experiments indicate that with Sephadex G-50 and distilled water as mobile phase, detection wavelength 220 nm, flow rate 1.5 mL/min, sample density 0.2 g/mL, and volume 0.2 mL are the optimal conditions. Bacteriostasis experiments of the fraction of purified peaks were carried out and the result was: peak 1>peak 3>peak 2; the molecular weight of peak 1 was about 3015 by high performance liquid chromatography; active peptide possessed positive charges by amino acid analysis, its cationic characteristics are in accordance with the nature of antimicrobial peptides.

  14. Chemical Composition and Antimicrobial Activity of Artemisiatschernieviana Besser from Iran

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    Masoud Kazemi

    2009-01-01

    Full Text Available The oil obtained from hydrodistillation of the aerial parts of Artemisia tschernieviana was analyzed by GC and GC/MS. The main constituents of the 30 identified components were p-cymene (21.3%, β-pinene (17.8%, α-pinene (9.4%, γ-terpinene (9.1%, (Z-cis-ocimene (8.8%, and α-cadinol (8.1%. This species is rich in monoterpenes. Antimicrobial activity was determined against six bacterial strains and one fungal strain. The results show that this oil is active against all the tested strains.

  15. ANTIMICROBIAL ACTIVITY OF DIFFERENT THIOSEMICARBAZONE COMPOUNDS AGAINST MICROBIAL PATHOGENS

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    Negi Parul

    2012-05-01

    Full Text Available Thiosemicarbazone belongs to a large group of thiourea derivatives, whose biological activities are a function of parent aldehyde or ketone moiety. They have been evaluated over the last 50 year as antiviral, antibacterial, antifungal, antimalarial, anticancer, leprosy, rheumatism, trypanosomiasis and coccidiodis. Thiosemicarbazones were prepared by simple process in which N4-thiosemicarbazone moiety was replaced by aliphatic, arylic and cyclic amines. Present study reported the anti-microbial activity of different thiosemicarbazone compounds against certain bacterial and fungal pathogens viz. Bacillus cereus, Staphylococcus epidermis, Moraxella cattarhalis, Staph. Saprophyticus, Candida albicans and Aspergillus flavans.

  16. Antimicrobial activity of oil from the root of Cinnamomum porrectum

    OpenAIRE

    Arunporn Itarat; Sopa Kummee; Souwalak Phongpaichit; Ladda Nilrat

    2007-01-01

    The steam-distilled oil from the root of Cinnamomum porrectum was tested for its antimicrobial activity against human pathogens including bacteria, yeasts and dermatophytes. It exhibited strongestactivity against Streptococcus mutans (MIC 0.01 mg/ml) followed by Candida albicans and dermatophytes (0.5-1.0 mg/ml), Bacillus subtilis (2 mg/ml), and susceptible strains of Staphylococcus aureus (4-16 mg/ml).It showed moderate activity against Cryptococcus neoformans (MIC 16-64 mg/ml) but no activi...

  17. STANDARDIZATION AND ANTIMICROBIAL ACTIVITY OF FICUS RELIGIOSA LINN. (FAMILY: MORACEAE

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    Jagtap Supriya

    2013-07-01

    Full Text Available Ficus religiosa Linn. (Moraceae has been traditionally claimed to be useful in asthmatic conditions, antidiarrhoeal, antiviral and astringent. It also shows antivenom activity. It is used in the treatment of various diseases such as cancer, inflammation or infectious diseases. In the present study, it includes standardization parameters which are carried out on leaves where successive soxhlet extraction of dried powdered leaves was carried out using petroleum ether, chloroform, methanol and water. All these extracts were subjected for in-vitro antimicrobial activity against the strains Escherichia coli and Staphylococcus aureus by cup plate method.

  18. Super-SERS-active and highly effective antimicrobial Ag nanodendrites

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    Li, H. B.; Liu, P.; Liang, Y.; Xiao, J.; Yang, G. W.

    2012-07-01

    We have developed simple and green electrochemistry to synthesize Ag nanostructures with high purity, good crystallinity and smooth surface for applications as super-SERS (surface-enhanced Raman scattering), SERS-active substrates and with highly effective antimicrobial activities. This synthesis takes place in a clean and slow reaction environment without any chemical additives, which ensures an ultrahigh active surface of the as-synthesized Ag nanostructures owing to their purity, good crystallinity and smooth morphology. Using this method, we synthesized nearly perfect Ag nanodendrites (NDs), which exhibit super-SERS sensitivity when they are used to detect the SERS spectra of rhodamine 6G at concentrations as low as 5 × 10-16 M, and have an ultrahigh electromagnetic (EM) enhancement factor of the order of 1013, breaking through the theoretical limit of EM enhancement. Meanwhile, the as-synthesized Ag NDs possess highly effective antimicrobial activities for Escherichia coli, Candida albicans and Staphylococcus aureus, which are over 10 times that of silver nanoparticles. Additionally, the basic physics and chemistry involved in the fabrication of Ag nanostructures are pursued. These investigations show that silver nanostructures with highly active surfaces can make the most of Ag nanostructures functioning as super-SERS-active substrates and multiple antibiotics.

  19. Evaluation of antimicrobial activity of selected plant extracts by rapid XTT colorimetry and bacterial enumeration.

    Science.gov (United States)

    Al-Bakri, Amal G; Afifi, Fatma U

    2007-01-01

    The aim of this study was to screen and evaluate the antimicrobial activity of indigenous Jordanian plant extracts, dissolved in dimethylsulfoxide, using the rapid XTT assay and viable count methods. XTT rapid assay was used for the initial screening of antimicrobial activity for the plant extracts. Antimicrobial activity of potentially active plant extracts was further assessed using the "viable plate count" method. Four degrees of antimicrobial activity (high, moderate, weak and inactive) against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, respectively, were recorded. The plant extracts of Hypericum triquetrifolium, Ballota undulata, Ruta chalepensis, Ononis natrix, Paronychia argentea and Marrubium vulgare had shown promising antimicrobial activity. This study showed that while both XTT and viable count methods are comparable when estimating the overall antimicrobial activity of experimental substances, there is no strong linear correlation between the two methods. PMID:16831479

  20. A new mesenchymal stem cell (MSC paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype.

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    Ruth S Waterman

    Full Text Available BACKGROUND: Our laboratory and others reported that the stimulation of specific Toll-like receptors (TLRs affects the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs. Toll-like receptors recognize "danger" signals, and their activation leads to profound cellular and systemic responses that mobilize innate and adaptive host immune cells. The danger signals that trigger TLRs are released following most tissue pathologies. Since danger signals recruit immune cells to sites of injury, we reasoned that hMSCs might be recruited in a similar way. Indeed, we found that hMSCs express several TLRs (e.g., TLR3 and TLR4, and that their migration, invasion, and secretion of immune modulating factors is drastically affected by specific TLR-agonist engagement. In particular, we noted diverse consequences on the hMSCs following stimulation of TLR3 when compared to TLR4 by our low-level, short-term TLR-priming protocol. PRINCIPAL FINDINGS: Here we extend our studies on the effect on immune modulation by specific TLR-priming of hMSCs, and based on our findings, propose a new paradigm for hMSCs that takes its cue from the monocyte literature. Specifically, that hMSCs can be polarized by downstream TLR signaling into two homogenously acting phenotypes we classify here as MSC1 and MSC2. This concept came from our observations that TLR4-primed hMSCs, or MSC1, mostly elaborate pro-inflammatory mediators, while TLR3-primed hMSCs, or MSC2, express mostly immunosuppressive ones. Additionally, allogeneic co-cultures of TLR-primed MSCs with peripheral blood mononuclear cells (PBMCs predictably lead to suppressed T-lymphocyte activation following MSC2 co-culture, and permissive T-lymphocyte activation in co-culture with MSC1. SIGNIFICANCE: Our study provides an explanation to some of the conflicting reports on the net effect of TLR stimulation and its downstream consequences on the immune modulating properties of stem cells. We further

  1. Antimicrobial properties and membrane-active mechanism of a potential α-helical antimicrobial derived from cathelicidin PMAP-36.

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    Yinfeng Lv

    Full Text Available Antimicrobial peptides (AMPs, which present in the non-specific immune system of organism, are amongst the most promising candidates for the development of novel antimicrobials. The modification of naturally occurring AMPs based on their residue composition and distribution is a simple and effective strategy for optimization of known AMPs. In this study, a series of truncated and residue-substituted derivatives of antimicrobial peptide PMAP-36 were designed and synthesized. The 24-residue truncated peptide, GI24, displayed antimicrobial activity comparable to the mother peptide PMAP-36 with MICs ranging from 1 to 4 µM, which is lower than the MICs of bee venom melittin. Although GI24 displayed high antimicrobial activity, its hemolytic activity was much lower than melittin, suggesting that GI24 have optimal cell selectivity. In addition, the crucial site of GI24 was identified through single site-mutation. An amino acid with high hydrophobicity at position 23 played an important role in guaranteeing the high antimicrobial activity of GI24. Then, lipid vesicles and whole bacteria were employed to investigate the membrane-active mechanisms. Membrane-simulating experiments showed that GI24 interacted strongly with negatively charged phospholipids and weakly with zwitterionic phospholipids, which corresponded well with the data of its biological activities. Membrane permeabilization and flow cytometry provide the evidence that GI24 killed microbial cells by permeabilizing the cell membrane and damaging membrane integrity. GI24 resulted in greater cell morphological changes and visible pores on cell membrane as determined using scanning electron microscopy (SEM and transmission electron microscope (TEM. Taken together, the peptide GI24 may provide a promising antimicrobial agent for therapeutic applications against the frequently-encountered bacteria.

  2. Absolute configuration and antimicrobial activity of acylhomoserine lactones.

    Science.gov (United States)

    Pomini, Armando M; Marsaioli, Anita J

    2008-06-01

    (S)-N-Heptanoylhomoserine lactone is an uncommon acyl odd-chain natural product employed by many Gram-negative bacteria as a signaling substance in chemical communication mechanisms known as quorum sensing. The absolute configuration determination of the metabolite produced by the phytopathogen Pantoea ananatis Serrano is reported herein. As with all other substances of this class, the lactone moiety possesses S configuration, corroborating the hypothesis that it shares the same biosynthetic pathway as the (S)-N-hexanoylhomoserine lactone and also that some LuxI homologues can accept both hexanoyl- and heptanoyl-ACP as precursors. Evaluation of the antimicrobial activity of enantiomeric acylhomoserine lactones against three Gram-positive bacteria (Bacillus cereus, B. subtilis, and Staphylococcus aureus) revealed important features between absolute configuration and antimicrobial activity. The N-heptanoylhomoserine lactone was considerably less active than the 3-oxo derivatives. Surprisingly, non-natural (R)-N-(3-oxo-octanoyl)homoserine lactone was as active as the S enantiomer against B. cereus, while the synthetic racemic product was less active than either enantiomer. PMID:18465897

  3. Antimicrobial activity of latex silver nanoparticles using Calotropis procera

    Institute of Scientific and Technical Information of China (English)

    Nadia Hussein Mohamed; Mady Ahmed Ismail; Wael Moustfa Abdel-Mageed

    2014-01-01

    Objective: To synthesize silver nanoparticles (AgNPs) by green methods using serum latex of Calotropis procera at 80 °C and evaluate them against bacteria, dermatophytes and phytopathogenic fungi comparing with the activity of untreated latex.Methods:The synthesis of AgNPs was performed by mixing 3% latex serum extract with the same volume of silver nitrate (2 mmol/L) solution in round flask and heating in water bath at 80 °C. Characterization of silver particles were determined using UV-vis spectrophotometer, transmission electron microscopy (TEM), X-ray diffraction and Fourier transform infrared spectroscopy. The antimicrobial activity of the green synthesized AgNPs was determined against bacteria, dermatophytes and phytopathogenic fungi and compared to the crude untreated latex by agar-well diffusion methods.Results:Biosynthesis of latex silver nanoparticles was successfully obtained by green method. The formation of AgNPs has been confirmed by UV-vis, TEM microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. TEM analysis showed that synthesized AgNPs are highly stable spherical shaped particles, well dispersed with a diameter ranged from 4 nm up to 25 nm and an average size of 12.33 nm. AgNPs showed strong antibacterial activity against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Serratia sp.) and antifungal activity against Trichophyton rubrum, Candida albicans and Aspergillus terreus.Conclusions:It can be concluded that serum latex of Calotropis procera was found to display strong potential for the synthesis of AgNPs as antimicrobial agents through rapid reduction of silver ions (Ag+ to Ag0). The green synthesized AgNPs were found to show higher antimicrobial efficacy than crude latex.

  4. Antimicrobial activity of latex silver nanoparticles using Calotropis procera

    Institute of Scientific and Technical Information of China (English)

    Nadia; Hussein; Mohamed; Mady; Ahmed; Ismail; Wael; Moustfa; Abdel-Mageed; Ahmed; Abdelfattah; Mohamed; Shoreit

    2014-01-01

    Objective:To synthesize silver nanoparticles(AgNPs) by green methods using scrum latex of Calotropis procera at 80 ℃ and evaluate them against bacteria,dermatophytes and phytopathogenic fungi comparing with the activity of untreated latex.Methods:The synthesis of AgNPs was performed by mixing 3%latex scrum extract with the same volume of silver nitrate(2 mmol/L) solution in round flask and heating in water bath at80 ℃.Characterization of silver particles were determined using UV-vis spectrophotometer,transmission electron microscopy(TEM),X-ray diffraction and Fourier transform infrared spectroscopy.The antimicrobial activity of the green synthesized AgNPs was determined against bacteria,dermatophytes and phytopathogenic fungi and compared to the crude untreated latex by agar-well diffusion methods.Results:Biosynthesis of latex silver nanoparticles was successfully obtained by green method.The formation of AgNPs has been confirmed by UV-vis,TEM microscopy.X-ray diffraction and Fourier transform infrared spectroscopy.TEM analysis showed that synthesized AgNPs are highly stable spherical shaped particles,well dispersed with a diameter ranged from 4 nm up to 25 nm and an average size of 12.33 nm.AgNPs showed strong antibacterial activity against Gram-negative bacteria(Escherichia coli,Pseudomonas aeruginosa and Serratia sp.) and antifungal activity against Trichophyton rubrum,Candida albicans and Aspergillus terreus.Conclusions:It can be concluded that serum latex of Calotropis pmcera was found to display strong potential for the synthesis of AgNPs as antimicrobial agents through rapid reduction of silver ions(Ag~+ to Ag~0).The green synthesized AgNPs were found to show higher antimicrobial efficacy than crude latex.

  5. Antimicrobial and antipathogenic activity of Fallopia japonica leaves alcoholic extract

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    Ioana-Cristina Marinaş

    2014-08-01

    Full Text Available The aim of the study consists in the investigation of the antimicrobial and antiphatogenic activity of ethanol extracts obtain from F. japonica leaves. Total phenolic content was determined by Folin-Ciocalteu method, while their phenolic composition was specified by HPLC. In vitro antimicrobial activity of various concentrations ranging from 6.25 to 200 μL/mL of alcoholic (ethanol 70% extract of F. japonica were analyzed on different clinical and reference bacterial strains (Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumanii and fungal strains belonging to Candida spp. using agar disk diffusion method and broth dilution method. The anti-pathogenic properties were studied by determining the adhesion capacity of microbial strains to inert substrate. The soluble virulence factors were quantified using specific media with different biochemical substrats for revealing haemolysins, lecithinase, gelatinase, lipase, DN-ase, amylase and iron chelating agents. The antibiogram adapted technique assesseded the synergic effects of F. japonica leaves extracts with the clinical used antibiotics for different bacterial strains. The studied extract showed the best antimicrobial activity against P. aeruginosa (6.25 μL/mL due to phenolic compound identified (epicatechin, rutin and quercetin. In the Gram-positive strains’ case were observed phenotypic changes in the DNA-ase and lechitinase enzymes expression. In the antibioresistance pattern profiling it was observed that F. japonica leaves improved the Kanamycin activity for S. aureus, Colistin for P. aeruginosa and Meropenem for A. baumanii. In this respect, could be assumed that this extract could be used complementarily with antibiotherapy, by inhibiting the specific virulence factors.

  6. Emerging concepts of how β-amyloid proteins and pro-inflammatory cytokines might collaborate to produce an 'Alzheimer brain' (Review).

    Science.gov (United States)

    Dal Pra, Ilaria; Chiarini, Anna; Pacchiana, Raffaella; Chakravarthy, Balu; Whitfield, James F; Armato, Ubaldo

    2008-01-01

    Three steps lead to the development of full-blown sporadic or late-onset Alzheimer's disease or dementia (AD). In the young brain, amyloid β-(1-42) (Aβ 42) is a normal aggregation-prone protein product of neuronal activity that is kept at a safe low level by proteolysis in neurons and glial cells, and by expulsion across the blood-brain barrier. But clearance declines with advancing age. Step 1: Because of the normal decline with age of the Aβ 42-clearing mechanisms, toxic amyloid-derived diffusible ligands (ADDLs) made of dodecamers of the aggregation-prone Aβ 42 start accumulating. These Aβ 42 dodecamers selectively target the initially huge numbers of excitatory synapses of neurons and cause them to start slowly dropping, which increasingly impairs plasticity and sooner or later starts noticeably affecting memory formation. At a certain point, this increasing loss of synapses induces the neurons to redirect their still-expressed cell cycle proteins from post-mitotic jobs, such as maintaining synapses, to starting a cell cycle and partially or completely replicating DNA without entering mitosis. The resulting aneuploid or tetraploid neurons survive for as long as 6-12 months as quasi-functional 'undead zombies', with developing tangles of hyperphosphorylated τ protein disrupting the vital anterograde axonal transport of mitochondria and other synapse-vital components. Step 2: The hallmark AD plaques appear as Aβ 42 clearance continues to decline and the formation of Aβ 42 non-diffusible fibrils begins in the aging brain. Step 3: A terminal cytokine-driven maëlstrom begins in the aging brain when microglia, the brain's professional macrophages, are activated in and around the plaques. They produce pro-inflammatory cytokines, such as IFN-γ, IL-1β and TNF-α. One of these, IFN-γ, causes the astrocytes enwrapping the neuronal synapses to express their β-secretase (BACE1) genes and produce and release Aβ 42, which can kill the closely apposed neurons by

  7. MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements

    Science.gov (United States)

    TROMBONE, Ana Paula Favaro; CAVALLA, Franco; SILVEIRA, Elcia Maria Varize; ANDREO, Camile Bermejo; FRANCISCONI, Carolina Favaro; FONSECA, Angélica Cristina; LETRA, Ariadne; SILVA, Renato Menezes; GARLET, Gustavo Pompermaier

    2016-01-01

    ABSTRACT Increased matrix metalloproteinases (MMPs) activity is a hallmark of periapical granulomas. However, the factors underlying the MMPs expression modulation in healthy and diseased periapical tissues remains to be determined. Objective In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo. Material and Methods MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotyping and N=26 for expression analysis). The Shapiro-Wilk, Fisher, Pearson, Chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant). Results The MMP1-1607 1G/2G and 1G/2G+2G/2G genotypes were significantly more prevalent in the patients than in controls, comprising a risk factor for periapical lesions development. MMP-1 mRNA levels were higher in periapical lesions than in healthy periodontal ligament samples, as well as higher in active than in inactive lesions. The polymorphic allele 2G carriers presented a significantly higher MMP-1 mRNA expression when compared with the 1G/1G genotype group. The ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of MMP-1. Additionally, the pro- and anti-inflammatory cytokines IL-17A, IFN-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression. Conclusion The MMP1-1607 SNP was identified as a risk factor for periapical lesions development, possibly due to its association with increased MMP-1 mRNA levels in periapical lesions. The MMP-1 expression is also under the control of the inflammatory milieu elements, being the

  8. Antimicrobial peptides in human sepsis

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    Lukas eMartin

    2015-08-01

    Full Text Available Nearly 100 years ago, antimicrobial peptides (AMPs were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP 1-3 and human beta-defensins (HBDs 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP -1-3 and HBD-2 in sepsis. The bactericidal/permeability increasing protein (BPI attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP-1-3, lactoferrin, BPI and heparin-binding protein (HBP are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11 possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin (talactoferrin alpha, TLF has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide (LPS. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe

  9. Antimicrobial, antioxidant activities and chemical composition of selected Thai spices

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    Juraithip Wungsintaweekul

    2010-12-01

    Full Text Available Nine volatile oils and six methanol extracts from Ocimum americanum, O. basilicum, O. sanctum, Citrus hystrix,Alpinia galanga, Curcuma zedoaria, Kaempferia parviflora and Zingiber cassumunar were assessed for antimicrobial andantioxidant activities. The volatile oils and extracts were investigated against eight bacteria and three fungi. The resultsillustrated that O. americanum volatile oil exhibited broad spectrum activity against tested bacteria with the MICs ranging1.4-3.6 mg/ml and Candida spp. with the MICs ranging from 0.5-0.6 mg/ml. The O. sanctum volatile oil showed a considerableactivity against only Candida spp. with the MICs ranging from 0.8-1.4 mg/ml. Interestingly, growth of Mycobacteriumphlei was inhibited by the volatiles of O. americanum, C. hystrix peel, and C. zedoaria with MIC of 1.7, 3.5 and 1.2 mg/ml,respectively. For antioxidant activity evaluation, the methanol extracts of C. hystrix (leaf and peel and K. parviflora hadpotent antioxidant activity by the radical-scavenging DPPH method with IC50 of 24.6, 66.3 and 61.5 mg/ml, respectively.GC-MS analysis revealed the typical chemical profiles of the volatile oils. The major component showed the characteristicsof the volatile oils and was probably responsible for the antimicrobial effect.

  10. Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities

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    C. S. Chidan Kumar

    2015-09-01

    Full Text Available A series of five new 2‐(1‐benzofuran‐2‐yl‐2‐oxoethyl 4-(un/substitutedbenzoates 4(a–e, with the general formula of C8H5O(C=OCH2O(C=OC6H4X, X = H, Cl, CH3, OCH3 or NO2, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a–e were characterized by FTIR, 1H-, 13C- and 1H-13C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34% in diphenyl-2-picrylhydrazyl (DPPH radical scavenging, 4d (31.01% ± 4.35% in ferric reducing antioxidant power (FRAP assay and 4a (27.11% ± 1.06% in metal chelating (MC activity.

  11. ANTIMICROBIAL ACTIVITY OF WHITE AND PINK NELUMBO NUCIFERA GAERTN FLOWERS

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    D.BRINDHA, D.ARTHI

    2013-09-01

    Full Text Available Nelumbo nucifera Gaertn (Family: Nelumbonaceae, medicinally versatile and used as an important raw material of age-old traditional medical practices like Ayurveda and folk medicine. Bioassays for antimicrobial activities were carried out using hydroethanolic extract of both white and pink flowers of Nelumbo nucifera Gaertn plant. Both the flower extracts were tested against five important bacterial strains and two fungal strains. Further, Minimum Inhibitory Concentration (MIC was evaluated against Escherichia coli (gram negative and Staphylococcus aureus (gram positive organisms. Both the flower extracts showed considerable activity against all tested bacteria and fungi strains. The white and pink flower extracts more or less showed similar antimicrobial activities. MIC for white flower extract against Escherichia coli and Staphylococcus aureus was found to be 430μg and 450μg respectively and pink flower showed 480μg and 490μg respectively. The antibacterial and antifungal activities of both flower extracts were comparable to those of selected chemical antibiotics suggesting their potential as alternatives to orthodox antibiotics in the treatment of infectious caused by these microorganisms.

  12. Antimicrobial activity of crude methanolic extracts from Ganoderma lucidum and Trametes versicolor

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    Lukáš Hleba

    2014-11-01

    Full Text Available In this paper the antimicrobial activity of crude methanolic extracts obtained from Ganoderma lucidum and Trametes versicolor were investigated. The antimicrobial activities of the extracts against E. coli, P. aeruginosa, S. epidermis, E. raffinosus, S. cerevisiae and C. albicans were determined by the microbroth dillution method according by EUCAST in 96-well microplates. Microorganisms were obtained from Czech Collection of Microorganisms. Absorbances after and before the experiment were subtracted, converted to binary system and obtained values to Probit analysis were used. Of the two macromycetes extracts tested, not all extracts showed antimicrobial activity in tested MICs range. The highest antimicrobial activity showed the both extracts to Saccharomyces cerevisiae. The less antimicrobial effects had the both macromycetes extracts to Staphylococcus epidermis. Antimicrobial activity of macromycetes methanolic crude extracts to others tested microorganisms showed no effect or used concentration could be higher.

  13. Quartz-Containing Ceramic Dusts: In vitro screening of the cytotoxic, genotoxic and pro-inflammatory potential of 5 factory samples

    Energy Technology Data Exchange (ETDEWEB)

    Ziemann, C; Creutzenberg, O [Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover (Germany); Jackson, P [CERAM Research Ltd., Stoke-on-Trent (United Kingdom); Brown, R [TOXSERVICES, Stretton (United Kingdom); Attik, G; Rihn, B H, E-mail: christina.ziemann@item.fraunhofer.d [Nancy-University, Faculte de Pharmacie, Nancy (France)

    2009-02-01

    Inhalation of some respirable crystalline silica (MMAD < approx. 4 mum) leads to inflammatory and malignant diseases. Comprehensive physicochemical/biological data and suitable in vitro/in vivo methods may distinguish between more or less harmful quartz-varieties. Within the European Collective Research Project SILICERAM an in vitro screening battery was established to evaluate cytotoxicity (LDH-release, MTT-assay), genotoxicity (Comet-assay) and pro-inflammatory potential (PGE{sub 2}-liberation, TNF-a mRNA expression) of 5 respirable quartz-containing dusts from ceramic plants: brickwork (BR: 7.8% quartz), tableware granulate/cast (TG/TC: 5.8%/3.1%), tiles (TI: 8.1%), refractory (RF: 3.7%). DQ12 (87% a-quartz) and Al{sub 2}O{sub 3} were used as particulate positive and negative controls, respectively. Primary rat alveolar macrophages and the macrophage cell line NR8383 served as model systems. Aluminium lactate was used as inhibitor of biologically active silica, enabling differentiation of silica- and non-specific toxicity. At 200mug/cm{sup 2} (2h) the dusts did not alter significantly LDH-release (except TC), whereas the MTT-assay demonstrated the mainly quartz-independent rank order: DQ12>RF>TG>Ti>BR>TC>Al{sub 2}O{sub 3}. DNA-damage was maximal for BR and TI followed by DQ12>TG>TC>RF>Al{sub 2}O{sub 3}. All dusts induced PGE{sub 2}-liberation (DQ12>BR>TC>TG>Ti>RF>Al{sub 2}O{sub 3}) at 50mug/cm{sup 2} (4h), but TNF-a mRNA (10mug/cm{sup 2}, 24h) was only increased by DQ12, TG (quartz-dependently), and TC. In conclusion, these in vitro tests were an adequate approach to screen the toxic potential of quartz-containing ceramic dusts, but the quartz-content was too low to differentiate the various quartz-varieties.

  14. Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells

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    Sutinen Elina M

    2012-08-01

    Full Text Available Abstract Background Alzheimer’s disease (AD involves increased accumulation of amyloid-β (Aβ plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18 in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. Methods We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP and its processing products, its cleaving enzymes, involved in amyloidogenic processing of APP, and markers of apoptosis. Results IL-18 increased protein levels of the β-site APP-cleaving enzyme BACE-1, the N-terminal fragment of presenilin-1 and slightly presenilin enhancer 2, both of which are members of the γ-secretase complex, as well as Fe65, which is a binding protein of the C-terminus of APP and one regulator for GSK-3β. IL-18 also increased APP expression and phosphorylation, which preceded increased BACE-1 levels. Further, IL-18 altered APP processing, increasing Aβ40 production in particular, which was inhibited by IL-18 binding protein. Increased levels of soluble APPβ were detected in culture medium after the IL-18 exposure. IL-18 also increased anti-apoptotic bcl-xL levels, which likely counteracted the minor increase of the pro-apoptotic caspase-3. Lactate dehydrogenase activity in culture medium was unaffected. Conclusions The IL-18 induction of BACE-1, APP processing, and Aβ is likely to be

  15. Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: New insights in atherosclerosis development.

    Science.gov (United States)

    Jarray, Rafika; Pavoni, Serena; Borriello, Lucia; Allain, Barbara; Lopez, Nicolas; Bianco, Sara; Liu, Wang-Qing; Biard, Denis; Demange, Luc; Hermine, Olivier; Garbay, Christiane; Raynaud, Françoise; Lepelletier, Yves

    2015-11-01

    Significant interest has recently emerged for phosphatase and actin regulatory protein (PHACTR1) gene in heart diseases prognosis. However, the functional role of phactr-1 protein remains elusive in heart related-diseases such as atherosclerosis, coronary artery calcification, ischaemic stroke, coronary artery stenosis and early-onset myocardial infarction. Phactr-1 is directly regulated by vascular endothelial growth factor A165 (VEGF-A165) through VEGF receptor 1 (VEGR-1) and Neuropilin-1 (NRP-1). Using an antagonist peptide approach to inhibit the interaction of VEGF-A165 to NRP-1 and VEGF-R1, we highlighted the importance of both cysteine residues located at the end of VEGF-A165 exon-7 and at the exon-8 to generate functional peptides, which decreased Phactr-1 expression. Here, we report original data showing Phactr-1 down-expression induces the expression of Matrix Metalloproteinase (MMP) regulators such as Tissue inhibitor of metalloproteinase (TIMP-1/-2) and Reversion-inducing-cysteine-rich protein with kazal motifs (RECK). Furthermore, focal adhesion kinases (FAK/PYK2/PAXILLIN) and metabolic stress (AMPK/CREB/eNOS) pathways were inhibited in endothelial cells. Moreover, the decrease of phactr-1 expression induced several factors implicated in atherosclerotic events such as oxidized low-density lipoprotein receptors (CD36, Clusterin, Cadherin-13), pro-inflammatory proteins including Thrombin, Thrombin receptor 1 (PAR-1), A Disintegrin And Metalloprotease domain-9/-17 (ADAM-9/-17), Trombospondin-2 and Galectin-3. Besides, Phactr-1 down-expression also induces emerging atherosclerosis biomarkers such as semicarbazide-sensitive amine oxidase (SSAO) and TGF-beta-inducible gene h3 (βIG-H3). In this report, we show for the first time the direct evidence of the phactr-1 biological function in the regulation of pro-atherosclerotic molecules. This intriguing result strengthened heart diseases PHACTR-1 single-nucleotide polymorphisms (SNP) correlation. Taken together

  16. Clinical findings and pro-inflammatory cytokines in dengue patients in Western India: a facility-based study.

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    D Priyadarshini

    Full Text Available BACKGROUND: Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF and 62 with Dengue hemorrhagic fever (DHF of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05. The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005 and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059. There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels. CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater

  17. Contribution of Pro-Inflammatory Cytokine Signaling within Midbrain Periaqueductal Gray to Pain Sensitivity in Parkinson's disease via GABAergic Pathway

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    Xianbo Zhuang

    2016-07-01

    Full Text Available Background/Aims: Hypersensitive pain response is often observed in patients with Parkinson's disease (PD; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs system of PAG in regulating exaggerated pain evoked by PD. Methods: We used a rat model of PD to perform the experimental protocols. PD was induced by microinjection of 6-hydroxydopamine to lesion the left medial forebrain bundle. Pain responses to mechanical and thermal stimulation were first examined in control rats and PD rats. Then, ELISA and Western Blot analysis were used to determine PIC levels and their receptors expression. Results: Protein expression of IL-1β, IL-6 and TNF-α receptors (namely, IL-1R, IL-6R and TNFR subtype TNFR1 in the plasma membrane PAG of PD rats was upregulated, whereas the total expression of PIC receptors was not significantly altered. The ratio of membrane protein and total protein (IL-1R, IL-6R and TNFR1 was 1.48±0.15, 1.59±0.18 and 1.67±0.16 in PAG of PD rats (P < 0.05 vs. their respective controls. This was accompanied with increases of PICs of PAG, and decreases of GABA (623±21 ng/mg in control rats and 418±18 ng/mg in PD rats; P < 0.05 vs. control rats and withdrawal thresholds to mechanical and thermal stimuli. Our data further showed that the concentrations of GABA and withdrawal thresholds were largely restored by blocking those PIC receptors in PAG of PD rats. Stimulation of GABA receptors in PAG of PD rats also blunted a decrease in withdrawal thresholds. Conclusions: Our data suggest that upregulation of the membrane PIC receptor in the PAG of PD rats is likely to impair the descending inhibitory pathways in regulating pain transmission

  18. Antimicrobial activity of some isatin-3--thiosemicarbazone complexes

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    SANDRA S. KONSTANTINOVIC

    2008-01-01

    Full Text Available Isatin-3-thiosemicarbazone complexes with Co(II, Ni(II, Cu(II, Zn(II, Hg(II and Pd(II were synthesized and evaluated for their antimicrobial activity against 7 pathogenic bacteria and 4 fungi. The complexes have an enhanced activity compared to the ligand due to transition metal involved in coordination. The anti-amoebic activity in vitro was evaluated against the HM1:IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The preliminary test results showed that the complexes had better anti-amoebic activity than their respective ligands. Moreover, the complexes showed better inhibition of the test organism.

  19. Isolation, identification and antimicrobial activity of propolis-associated fungi.

    Science.gov (United States)

    de Souza, Giovanni Gontijo; Pfenning, Ludwig Heinrich; de Moura, Fabiana; Salgado, Mírian; Takahashi, Jacqueline Aparecida

    2013-01-01

    Propolis is a natural product widely known for its medicinal properties. In this work, fungi present on propolis samples were isolated, identified and tested for the production of antimicrobial metabolites. Twenty-two fungal isolates were obtained, some of which were identified as Alternaria alternata, Aspergillus flavus, Bipolaris hawaiiensis, Fusarium merismoides, Lasiodiplodia theobromae, Penicillium citrinum, Penicillium crustosum, Penicillium janthinellum, Penicillium purpurogenum, Pestalotiopsis palustris, Tetracoccosporium paxianum and Trichoderma koningii. These fungi were grown in liquid media to obtain crude extracts that were evaluated for their antibiotic activity against pathogenic bacteria, yeast and Cladosporium cladosporioides and A. flavus. The most active extract was obtained from L. theobromae (minimum inhibitory concentration = 64 μg/mL against Listeria monocitogenes). Some extracts showed to be more active than the positive control in the inhibition of Staphylococcus aureus and L. monocitogenes. Therefore, propolis is a promising source of fungi, which produces active agents against relevant food poisoning bacteria and crop-associated fungi.

  20. Chemical constituents, antimicrobial and antimalarial activities of Zanthoxylum monophyllum.

    Science.gov (United States)

    Rodríguez-Guzmán, Raquel; Fulks, Laura C Johansmann; Radwan, Mohamed M; Burandt, Charles L; Ross, Samir A

    2011-09-01

    From the leaves and bark of Zanthoxylum monophyllum, a new lignan, 3-methoxy-3',4'-methylenedioxylignan-4,8,9,9'-tetraol (1), has been isolated along with 22 known compounds (2- 23), fifteen of them reported for the first time from Z. monophyllum. Their chemical structures were elucidated using detailed spectroscopic studies and chemical analysis. All compounds were evaluated for antimicrobial and antiprotozoal activities. Alkaloids BIS-[6-(5,6-dihydro-chelerythrinyl)] ether (2) and 6-ethoxy-chelerythrine (4) exhibited strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA). Compound 4-methoxy-N-methyl-2-quinolone (9) exhibited significant activity against MRSA (IC50 value of 8.0 µM) while compound 5,8,4'-trihydroxy-3,7,3'-trimethoxyflavone (10) showed weak activity against Plasmodium falciparum.

  1. SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF NEW PYRAZOLOPYRIDAZINE DERIVATIVES

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    Mahfuz Alam

    2015-03-01

    Full Text Available Several new pryrazolo-pyridazine derivatives (4a-h were synthesized through multi-step synthesis and evaluated for their antimicrobial activities. In the first step, 6-phenyl-2,3,4,5-tetrahydropyridazin-3-one (2 was prepared by reacting 4-(4-chlorophenyl-4-oxobutanoic acid (1 with hydrazine hydrate. Then, aryl-aldehydes were reacted with 2 to furnish pyridazinone derivatives (3a-g. Finally, pyridazinones (3a-h were reacted with hydrazine hydrate to furnish the title compounds (4a-h. The newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities against six microbial strains. Compounds 4d, 4e and 4f exhibited significant antibacterial action, whereas compounds 4c and 4d showed potential antifungal activity. Compound 4d, 5-(4-Chlorophenyl-3-(4-fluorophenyl-3,3a,4,7-tetrahydro-2H-pyrazolo[3,4- ]pyridazine, emerged as lead compound having broad spectrum of antimicrobial action.

  2. Antimicrobial activities of essential oil from Artemisiae argyi leaves

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; ZHANG Xue-ke; WU Nan; FU Yu-jie; ZU Yuan-gang

    2006-01-01

    A study was conducted to determine the antimicrobial activities of essential oil from Artemisiae argyi leaves. The sample of the essential oil was analyzed by GC-MS. From 18 compounds representing the oils, Eucalyptole (18.42%), Spathulenol (14.32), 4-Methyl-1-(1-methylethyl)-3-cyclohexen-1-ol (3.10%), 3-Carene (2.64%) appeared as the main components. The screening of antimicro bial activity of the essential oil was evaluated using agar diffusion and broth microdilution methods. Gram-positive bacterial were more sensitive than gram-negative bacterial of the 8 microorganisms, and Staphylococcus aureus ATCC 6538 showed the lowest MIC (0.3125%) and MBC (0.625%). In the disc diffusion assay, Staphylococcus epidermidis ATCC 49134 and Bacillus subtilis ATCC 6633 showed obvious inhibitory activity. Survival curve showed that, 2MIC ofArtemisiae argyi essential oil had a lethal effect on Candida albicans within the first 1 h. Results presented here suggest that the essential oil of Artemisiae argyi leaves possesses antimicrobial properties, and provides scientific foundations for exploition ofArtemisiae argyi.

  3. Antimicrobial Activity of Starch Hydrogel Incorporated with Copper Nanoparticles.

    Science.gov (United States)

    Villanueva, María Emilia; Diez, Ana María Del Rosario; González, Joaquín Antonio; Pérez, Claudio Javier; Orrego, Manuel; Piehl, Lidia; Teves, Sergio; Copello, Guillermo Javier

    2016-06-29

    In order to obtain an antimicrobial gel, a starch-based hydrogel reinforced with silica-coated copper nanoparticles (Cu NPs) was developed. Cu NPs were synthesized by use of a copper salt and hydrazine as a reducing agent. In order to enhance Cu NP stability over time, they were synthesized in a starch medium followed by a silica coating. The starch hydrogel was prepared by use of urea and water as plasticizers and it was treated with different concentrations of silica-coated copper nanoparticles (Si-Cu NPs). The obtained materials were characterized by Fourier transform infrared (FT-IR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, scanning electron microscopy (SEM), and rheometry. FT-IR and EPR spectra were used for characterization of Cu NPs and Si-Cu NPs, confirming that a starch cap was formed around the Cu NP and demonstrating the stability of the copper nanoparticle after the silica coating step. SEM images showed Cu NP, Si-Cu NP, and hydrogel morphology. The particle size was polydisperse and the structure of the gels changed along with particle concentration. Increased NP content led to larger pores in starch structure. These results were in accordance with the rheological behavior, where reinforcement by the Si-Cu NP was seen. Antimicrobial activity was evaluated against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial species. The hydrogels were demonstrated to maintain antimicrobial activity for at least four cycles of use. A dermal acute toxicity test showed that the material could be scored as slightly irritant, proving its biocompatibility. With these advantages, it is believed that the designed Si-Cu NP loaded hydrogel may show high potential for applications in various clinical fields, such as wound dressings and fillers.

  4. INVESTIGATION OF ANTIMICROBIAL AND ANTI-INFLAMMATORY ACTIVITY OF CURCUMA LONGA

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    Mohammad Basir Khan , Md. Atai Rabby , Md Hasmat Ullah and Chowdhury Faiz Hossain*

    2013-03-01

    Full Text Available ABSTRACT: Turmeric (Curcuma longa is a rhizomatous herbaceous perennial plant used as a food additive. It has been reported that rhizome of this plant have antibacterial, antifungal, anti-inflammatory, antioxidant and antitumor property. Methanol extract of Rhizome of Curcuma longa was investigated here to see the antimicrobial actions and anti-inflammatory effect. During the extraction process a purified single compound (D1 was isolated and investigated for its antimicrobial activity. Significant antimicrobial activity than penicillin were found for 500µg C. longa extract. Anti-inflammatory action of C. longa was also assessed using mice models. The purified compound D1 fraction showed antimicrobial action in 50µg concentration. Our study reveal that C. longa has antimicrobial activity against various gram positive and gram negative bacteria where curcumin may not be the only compound that is responsible for the antimicrobial activity. On the other hand, C. longa extract had shown significant anti-inflammatory action.

  5. New perspectives for natural antimicrobial peptides: application as antinflammatory drugs in a murine model

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    Capparelli Rosanna

    2012-11-01

    Full Text Available Abstract Background Antimicrobial peptides (AMPs are an ancient group of defense molecules. AMPs are widely distributed in nature (being present in mammals, birds, amphibians, insects, plants, and microorganisms. They display bactericidal as well as immunomodulatory properties. The aim of this study was to investigate the antimicrobial and anti-inflammatory activities of a combination of two AMPs (temporin B and the royal jellein I against Staphylococcus epidermidis. Results The temporin B (TB-KK and the royal jelleins I, II, III chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C, were tested for their activity against 10 different Staphylococcus epidermidis strains, alone and in combination. Of the three royal jelleins, RJI-C showed the highest activity. Moreover, the combination of RJI-C and TB-KK (MIX displayed synergistic activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-α and IFN-γ to the same extent as acetylsalicylic acid. In vivo, the MIX sterilized mice infected with Staphylococcus epidermidis in eleven days and inhibited the expression of genes encoding the prostaglandin-endoperoxide synthase 2 (COX-2 and CD64, two important parameters of inflammation. Conclusion The study shows that the MIX – a combination of two naturally occurring peptides - displays both antimicrobial and anti-inflammatory activities.

  6. Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives.

    Science.gov (United States)

    Patel, Chandani; Bassin, Jatinder P; Scott, Mark; Flye, Jenna; Hunter, Ann P; Martin, Lee; Goyal, Madhu

    2016-01-01

    A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25-600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position. PMID:27376253

  7. Essential Oil Prepared from Cymbopogon citrates Exerted an Antimicrobial Activity Against Plant Pathogenic and Medical Microorganisms

    OpenAIRE

    Jeong, Mi-Ran; Park, Pyeong Beom; Kim, Dae-Hyuk; Jang, Yong-Suk; Jeong, Han Sol; Choi, Sang-Hoon

    2009-01-01

    Essential oils are mixtures of volatile, lipophilic compounds originating from plants. Some essential oils have useful biological activities including antimicrobial, spasmolytic, antiplasmodial, and insect-repelling activities. In this study, we tested the antimicrobial activity of essential oil prepared from the aromatic plant, Cymbopogon citrates, against three important plant pathogenic and medical microorganisms, Pectobacterium carotovorum, Colletotrichum gloeosporioides, and Aspergillus ...

  8. In vitro antimicrobial activity of pistachio (Pistacia vera L.) polyphenols.

    Science.gov (United States)

    Bisignano, Carlo; Filocamo, Angela; Faulks, Richard M; Mandalari, Giuseppina

    2013-04-01

    We investigated the antimicrobial properties of polyphenol-rich fractions derived from raw shelled and roasted salted pistachios. American Type Culture Collection (ATCC), food and clinical isolates, of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Pseudomonas mirabilis), Gram-positive bacteria (Listeria monocytogenes, Enterococcus hirae, Enterococcus faecium, Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus), the yeasts Candida albicans and Candida parapsilosis and the fungus Aspergillus niger were used. Pistachio extracts were active against Gram-positive bacteria with a bactericidal effect observed against L. monocytogenes (ATCC strains and food isolates), S. aureus and MRSA clinical isolates. Extracts from raw shelled pistachios were more active than those from roasted salted pistachios. The bactericidal activity of pistachio extracts could be used to help control the growth of some microorganisms in foods to improve safety and may find application as a topical treatment for S. aureus.

  9. Synthesis, Characterization and antimicrobial activity of Cyanopyridine derivatives with Vanillin.

    Directory of Open Access Journals (Sweden)

    K. N. Borkhataria

    2014-02-01

    Full Text Available Cyanopyridines play a vital role owing to their range of biological and physiological activities. In the light of these biological activities and variety of industrial applications, some new of 6-Aryl-4-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-2-methoxy-3-cyanopyridines (1a-l & 6-Aryl-4-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-2-ethoxy-3-cyanopyridine (2a-l have been prepared, by the cyclocondensation of 1-Aryl-3-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-propenones type (I with malononitrile in presence of Sodiummethoxide & Sodiumethoxide. All the prepared compounds were characterized by their spectral (I.R., N.M.R. ,Mass data and screened for their antimicrobial activities.

  10. SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF DICHOTOMIN A ANALOGS

    Directory of Open Access Journals (Sweden)

    Himaja Malipeddi

    2010-09-01

    Full Text Available A solution phase peptide synthesis was employed to synthesize Dichotomin A analogs. The N, O-dimethylation on Tyrosine and configurational change of L- to D- on Valine was made on Dichotomin A to derive the compounds 1 Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3, O-CH3 Tyr-Val] and 2 Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3,O-CH3Tyr-D-Val]. The structure of these compounds was confirmed by IR, 1H NMR, and FABMASS. The synthesized compounds were tested for their biological activities against bacterial and fungal organisms and were found to be active. Compound (2 carrying D-valine unit have shown more antimicrobial activity than the compound carrying L-valine unit.

  11. In vitro antimicrobial activity of pistachio (Pistacia vera L.) polyphenols.

    Science.gov (United States)

    Bisignano, Carlo; Filocamo, Angela; Faulks, Richard M; Mandalari, Giuseppina

    2013-04-01

    We investigated the antimicrobial properties of polyphenol-rich fractions derived from raw shelled and roasted salted pistachios. American Type Culture Collection (ATCC), food and clinical isolates, of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Pseudomonas mirabilis), Gram-positive bacteria (Listeria monocytogenes, Enterococcus hirae, Enterococcus faecium, Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus), the yeasts Candida albicans and Candida parapsilosis and the fungus Aspergillus niger were used. Pistachio extracts were active against Gram-positive bacteria with a bactericidal effect observed against L. monocytogenes (ATCC strains and food isolates), S. aureus and MRSA clinical isolates. Extracts from raw shelled pistachios were more active than those from roasted salted pistachios. The bactericidal activity of pistachio extracts could be used to help control the growth of some microorganisms in foods to improve safety and may find application as a topical treatment for S. aureus. PMID:23350629

  12. ANTIOXIDANT, CYTOTOXIC AND ANTIMICROBIAL ACTIVITY OF SONNERATIA ALBA BARK

    Directory of Open Access Journals (Sweden)

    Md. Ali Milon*1, Md. Abdul Muhit , Durajan Goshwami , Mohammad Mehedi Masud and Bilkis Begum

    2012-07-01

    Full Text Available The present study was undertaken to evaluate antioxidant, cytotoxic and antimicrobial activity of Sonneratia alba bark. The carbon tetrachloride, chloroform soluble partitionate of methanolic extract and crude methanolic extract showed significant antioxidant property using 1,1-diphenyl-2-pecrylhydrazyl(DPPH scavenging assay ,of which chloroform partitionate and crude extract demonstrated highest activity with IC50 value of 12µg/ml and 14µg/ml respectively. In the brine shrimp lethality bioassay, LC50 values obtained from the best fit line slope were 0.812, 14.94, 0.831 and 3.288 µg/ml for standard (Vincristine sulphate, n-Hexane, carbon tetrachloride and chloroform soluble partitionate of methanolic extract respectively. The carbon tetrachloride soluble fraction revealed moderate activities against Bacillus cereus, Bacillus subtilis, Sarcina lutea, Pseudomonas aeruginosa and Shigella dysenteriae test organisms.

  13. Synthesis, DNA interaction and antimicrobial activities of three rimantadine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bing-Mi; Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Xin, E-mail: wangxinlnu@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Li-Ping; Liu, Yang [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Niu, Hua-Ying [Jinan Dachpharm Development Co., Ltd., Jinan 250100 (China); Liu, Bin, E-mail: liubinzehao@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)

    2015-03-15

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method.

  14. Antimicrobial activity of ginkgo biloba leaf extract on aeromonas hydrophila

    International Nuclear Information System (INIS)

    The effect of ginkgo biloba extract leaf (GBE) on growth and production of haemolysin by A. hydrophila at 4 deg C, 28 deg C, and 37 deg C was investigated as well as the effect of gamma irradiation on antimicrobial activity of ginkgo biloba leaf extract. A. hydrophila grown at 37 deg C for 24 h was inoculated (about 6 log cfu/ml) into TSB broth containing various GBE concentrations of 0.1,0.25,0.5,1,2.5,5.0, 7.5, 10.0, 15.0, or 20.0% and stored at 4 deg C, 28 deg C, and 37 deg C. The inhibitory effect of the GBE was more pronounced at low temperature of 4 deg C. A total of 5% GBE was necessary to inhibit A. hydrophila at 4 deg C, whereas 7.5% inhibited the bacteria at 28 deg C, and 10 % inhibited the bacteria at 37 deg C. Addition of GBE affected the growth and haemolysin production of the pathogen in varying degrees compared to the control . Also , it is evident that gamma irradiation of GBE up to 25 kGy did not change its antimicrobial activity during 72 h at 28 deg C

  15. Antimicrobial activity of Uncaria tomentosa against oral human pathogens.

    Science.gov (United States)

    Ccahuana-Vasquez, Renzo Alberto; Santos, Silvana Soléo Ferreira dos; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2007-01-01

    Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria tomentosa was tested in vitro to determine the minimum inhibitory concentration (MIC) on selected microbial strains. The tested strains were oral clinical isolates of Streptococcus mutans, Staphylococcus spp., Candida albicans, Enterobacteriaceae and Pseudomonas aeruginosa. The tested concentrations of Uncaria tomentosa ranged from 0.25-5% in Müeller-Hinton agar. Three percent Uncaria tomentosa inhibited 8% of Enterobacteriaceae isolates, 52% of S. mutans and 96% of Staphylococcus spp. The tested concentrations did not present inhibitory effect on P. aeruginosa and C. albicans. It could be concluded that micropulverized Uncaria tomentosa presented antimicrobial activity on Enterobacteriaceae, S. mutans and Staphylococcus spp. isolates.

  16. Evidence for antimicrobial activity associated with common house spider silk

    Directory of Open Access Journals (Sweden)

    Wright Simon

    2012-06-01

    Full Text Available Abstract Background Spider silk is one of the most versatile materials in nature with great strength and flexibility. Native and synthetically produced silk has been used in a wide range of applications including the construction of artificial tendons and as substrates for human cell growth. In the literature there are anecdotal reports that suggest that native spider silk may also have antimicrobial properties. Findings In this study we compared the growth of a Gram positive and a Gram negative bacterium in the presence and absence of silk produced by the common house spider Tegenaria domestica. We demonstrate that native web silk of Tegenaria domestica can inhibit the growth of the Gram positive bacterium, Bacillus subtilis. No significant inhibition of growth was detected against the Gram negative bacterium, Escherichia coli. The antimicrobial effect against B. subtilis appears to be short lived thus the active agent potentially acts in a bacteriostatic rather than bactericidal manner. Treatment of the silk with Proteinase K appears to reduce the ability to inhibit bacterial growth. This is consistent with the active agent including a protein element that is denatured or cleaved by treatment. Tegenaria silk does not appear to inhibit the growth of mammalian cells in vitro thus there is the potential for therapeutic applications.

  17. HLA-B27-homodimer-specific antibody modulates the expansion of pro-inflammatory T-cells in HLA-B27 transgenic rats

    OpenAIRE

    Osiris Marroquin Belaunzaran; Sascha Kleber; Stefan Schauer; Martin Hausmann; Flora Nicholls; Maries Van den Broek; Sravan Payeli; Adrian Ciurea; Simon Milling; Frank Stenner; Jackie Shaw; Simon Kollnberger; Paul Bowness; Ulf Petrausch; Christoph Renner

    2015-01-01

    Objectives: HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorder...

  18. Development of post-pericardiotomy syndrome is preceded by an increase in pro-inflammatory and a decrease in anti-inflammatory serological markers

    Directory of Open Access Journals (Sweden)

    Snefjellå Nora

    2012-07-01

    Full Text Available Abstract The post-pericardiotomy syndrome (PPS is a common complication after cardiac surgery, occuring in 10-40% of patients. PPS may prolong hospitalization, and even serious complications like tamponade and constrictive pericarditis may occur. Early diagnosis and treatment may reduce morbidity. In 50 patients transferred to our hospital after cardiac surgery we found an increase in pro-inflammatory and a decrease in anti-inflammatory cytokines at admission in the patients later developing PPS compared to the patients who did not develop PPS. If confirmed in larger studies, these findings may prove useful in early identification of and targeted treatment in patients developing PPS.

  19. Antimicrobial activity of extracts from Tamarindus indica L. leaves

    Directory of Open Access Journals (Sweden)

    Julio Cesar Escalona-Arranz

    2010-01-01

    Full Text Available Tamarindus indica L. leaves are reported worldwide as antibacterial and antifungal agents; however, this observation is not completely accurate in the case of Cuba. In this article, decoctions from fresh and sun dried leaves, as well as fluid extracts prepared with 30 and 70% ethanol-water and the pure essential oil from tamarind leaves were microbiologically tested against Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomona aeruginosa and Candida albicans. Aqueous and fluid extracts were previously characterized by spectrophotometric determination of their total phenols and flavonoids, while the essential oil was chemically evaluated by gas chromatography/mass spectroscopy (GC/MS. Experimental data suggest phenols as active compounds against B. subtilis cultures, but not against other microorganisms. On the other hand, the essential oil exhibited a good antimicrobial spectrum when pure, but its relative low concentrations in common folk preparations do not allow for any good activity in these extracts.

  20. Antimicrobial activity of extracts from Tamarindus indica L. leaves.

    Science.gov (United States)

    Escalona-Arranz, Julio César; Péres-Roses, Renato; Urdaneta-Laffita, Imilci; Camacho-Pozo, Miladis Isabel; Rodríguez-Amado, Jesús; Licea-Jiménez, Irina

    2010-07-01

    Tamarindus indica L. leaves are reported worldwide as antibacterial and antifungal agents; however, this observation is not completely accurate in the case of Cuba. In this article, decoctions from fresh and sun dried leaves, as well as fluid extracts prepared with 30 and 70% ethanol-water and the pure essential oil from tamarind leaves were microbiologically tested against Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomona aeruginosa and Candida albicans. Aqueous and fluid extracts were previously characterized by spectrophotometric determination of their total phenols and flavonoids, while the essential oil was chemically evaluated by gas chromatography/mass spectroscopy (GC/MS). Experimental data suggest phenols as active compounds against B. subtilis cultures, but not against other microorganisms. On the other hand, the essential oil exhibited a good antimicrobial spectrum when pure, but its relative low concentrations in common folk preparations do not allow for any good activity in these extracts.

  1. Antimicrobial activity of diterpenes from Viguiera arenaria against endodontic bacteria.

    Science.gov (United States)

    Carvalho, Tatiane C; Simão, Marília R; Ambrósio, Sérgio R; Furtado, Niege A J C; Veneziani, Rodrigo C S; Heleno, Vladimir C G; Da Costa, Fernando B; Gomes, Brenda P F A; Souza, Maria Gorete M; Borges dos Reis, Erika; Martins, Carlos H G

    2011-01-01

    Six pimarane-type diterpenes isolated from Viguiera arenaria Baker and two semi-synthetic derivatives were evaluated in vitro against a panel of representative microorganisms responsible for dental root canal infections. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Prevotella buccae, Fusobacterium nucleatum, Bacteroides fragilis, Actinomyces naeslundii, Actinomyces viscosus, Peptostreptococcus micros, Enterococcus faecalis and Aggregatibacter actinomycetemcomitans. The compounds ent-pimara-8(14),15-dien-19-oic acid, its sodium salt and ent-8(14),15-pimaradien-3β-ol were the most active, displaying MIC values ranging from 1 to 10 μg mL-1. The results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new chemicals for use as a complement to instrumental endodontic procedures. PMID:21233793

  2. Antimicrobial Activity of Diterpenes from Viguiera arenaria against Endodontic Bacteria

    Directory of Open Access Journals (Sweden)

    Carlos H. G. Martins

    2011-01-01

    Full Text Available Six pimarane-type diterpenes isolated from Viguiera arenaria Baker and two semi-synthetic derivatives were evaluated in vitro against a panel of representative microorganisms responsible for dental root canal infections. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC against Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Prevotella buccae, Fusobacterium nucleatum, Bacteroides fragilis, Actinomyces naeslundii, Actinomyces viscosus, Peptostreptococcus micros, Enterococcus faecalis and Aggregatibacter actinomycetemcomitans. The compounds ent-pimara-8(14,15-dien-19-oic acid, its sodium salt and ent-8(14,15-pimaradien-3β-ol were the most active, displaying MIC values ranging from 1 to 10 μg mL-1. The results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new chemicals for use as a complement to instrumental endodontic procedures.

  3. Semisynthetic Modification of Cedrelone and its Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    P. Malairajana

    2012-12-01

    Full Text Available Cedrelone was isolated from Toona ciliata heart wood and the compound was modified with various chemical reagents and the resultant product was characterized by IR, 1H NMR, 13C NMR and Mass spectra. The synthesized compounds were screened for antimicrobial activities and the zone of inhibition was ascertained by disc diffusion method. The microorganisms selected for the study was Gram positive organisms such as a Staphylococcus aureus (ATCC 9144, b Staphylococcus epidermitis (ATCC 155, c Bacillus subtilis (ATCC 6633, d Bacillus cereus (ATCC 11778, e Micrococcus luteus (ATCC 46789 and Gram negative organisms a Escherichia coli (ATCC 25922, b Pseudomonas aeruginosa (ATCC 9027. Fungi organism a Candida albicans (ATCC 1091, b Aspergillus niger (ATCC 6275. Cedrelone and its derivatives exerted pronounced inhibitory response against all the species of bacterial organism tested, except E. coli. Bromohydroxy cedrelone and Michael adduct showed good antifungal activity.

  4. Insights into Animal and Plant Lectins with Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Renata de Oliveira Dias

    2015-01-01

    Full Text Available Lectins are multivalent proteins with the ability to recognize and bind diverse carbohydrate structures. The glyco -binding and diverse molecular structures observed in these protein classes make them a large and heterogeneous group with a wide range of biological activities in microorganisms, animals and plants. Lectins from plants and animals are commonly used in direct defense against pathogens and in immune regulation. This review focuses on sources of animal and plant lectins, describing their functional classification and tridimensional structures, relating these properties with biotechnological purposes, including antimicrobial activities. In summary, this work focuses on structural-functional elucidation of diverse lectin groups, shedding some light on host-pathogen interactions; it also examines their emergence as biotechnological tools through gene manipulation and development of new drugs.

  5. Antimicrobial activity of extracts from Tamarindus indica L. leaves.

    Science.gov (United States)

    Escalona-Arranz, Julio César; Péres-Roses, Renato; Urdaneta-Laffita, Imilci; Camacho-Pozo, Miladis Isabel; Rodríguez-Amado, Jesús; Licea-Jiménez, Irina

    2010-07-01

    Tamarindus indica L. leaves are reported worldwide as antibacterial and antifungal agents; however, this observation is not completely accurate in the case of Cuba. In this article, decoctions from fresh and sun dried leaves, as well as fluid extracts prepared with 30 and 70% ethanol-water and the pure essential oil from tamarind leaves were microbiologically tested against Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomona aeruginosa and Candida albicans. Aqueous and fluid extracts were previously characterized by spectrophotometric determination of their total phenols and flavonoids, while the essential oil was chemically evaluated by gas chromatography/mass spectroscopy (GC/MS). Experimental data suggest phenols as active compounds against B. subtilis cultures, but not against other microorganisms. On the other hand, the essential oil exhibited a good antimicrobial spectrum when pure, but its relative low concentrations in common folk preparations do not allow for any good activity in these extracts. PMID:20931087

  6. Antimicrobial activity of extracts from Tamarindus indica L. leaves

    Science.gov (United States)

    Escalona-Arranz, Julio César; Péres-Roses, Renato; Urdaneta-Laffita, Imilci; Camacho-Pozo, Miladis Isabel; Rodríguez-Amado, Jesús; Licea-Jiménez, Irina

    2010-01-01

    Tamarindus indica L. leaves are reported worldwide as antibacterial and antifungal agents; however, this observation is not completely accurate in the case of Cuba. In this article, decoctions from fresh and sun dried leaves, as well as fluid extracts prepared with 30 and 70% ethanol-water and the pure essential oil from tamarind leaves were microbiologically tested against Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomona aeruginosa and Candida albicans. Aqueous and fluid extracts were previously characterized by spectrophotometric determination of their total phenols and flavonoids, while the essential oil was chemically evaluated by gas chromatography/mass spectroscopy (GC/MS). Experimental data suggest phenols as active compounds against B. subtilis cultures, but not against other microorganisms. On the other hand, the essential oil exhibited a good antimicrobial spectrum when pure, but its relative low concentrations in common folk preparations do not allow for any good activity in these extracts. PMID:20931087

  7. Antimicrobial Activity of Catharanthus roseus – A Detailed Study

    Directory of Open Access Journals (Sweden)

    Prajakta J. Patil

    2010-06-01

    Full Text Available Catharanthus roseus (periwinkle is an important medicinal plant for novel pharmaceuticals since most of the bacterial pathogens are developing resistance against many of the currently available anti microbial drugs. Plants have proved to be significant natural resources for effective chemotherapeutic agents and offering a broad spectrum of activity with greater emphasis on preventive action. This study aims to investigate some of the anti microbial properties of this plant. The anticancer properties of Catharanthus roseus has been the major interest in all investigations. The antimicrobial activity has been checked against microorganisms like Pseudomonas aeruginosa NCIM 2036, Salmonella typhimurium NCIM 2501, Staphylococcus aureus NCIM 5021. The findings show that the extracts from the leaves of this plant can be used as prophylactic agent in many of the diseases, which sometime are of the magnitude of an epidemic.

  8. Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection

    Science.gov (United States)

    Melvin, Jeffrey A.; Lashua, Lauren P.; Kiedrowski, Megan R.; Yang, Guanyi; Deslouches, Berthony; Montelaro, Ronald C.

    2016-01-01

    ABSTRACT Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms

  9. Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection.

    Science.gov (United States)

    Melvin, Jeffrey A; Lashua, Lauren P; Kiedrowski, Megan R; Yang, Guanyi; Deslouches, Berthony; Montelaro, Ronald C; Bomberger, Jennifer M

    2016-01-01

    Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms formed by the

  10. Differential activity of innate defense antimicrobial peptides against Nocardia species

    Directory of Open Access Journals (Sweden)

    Wagner Dirk

    2010-02-01

    Full Text Available Abstract Background Members of the genus Nocardia are ubiquitous environmental saprophytes capable to cause human pulmonary, disseminated and cutaneous nocardiosis or bovine mastitis. Innate immunity appears to play an important role in early defense against Nocardia species. To elucidate the contribution of antimicrobial peptides (AMPs in innate defense against Nocardia, the activity of human α-defensins human neutrophil peptides (HNPs 1-3, human β-defensin (hBD-3 and cathelicidin LL-37 as well as bovine β-defensins lingual and tracheal antimicrobial peptides (LAP, TAP and bovine neutrophil-derived indolicidin against four important Nocardia species was investigated. Results Whereas N. farcinica ATCC 3318 and N. nova ATCC 33726 were found to be susceptible to all investigated human and bovine AMPs, N. asteroides ATCC 19247 was killed exclusively by neutrophil-derived human α-defensins HNP 1-3 and bovine indolicidin. N. brasiliensis ATCC 19296 was found to exhibit complete resistance to investigated human AMPs and to be susceptible only to bovine indolicidin. Conclusion Selected AMPs are capable to contribute to the first line of defense against Nocardia, yet, susceptibility appears to vary across different Nocardia species. Obtained results of neutrophil-derived AMPs to possess the broadest antinocardial spectrum are remarkable, since nocardiosis is characterized by a neutrophil-rich infiltrate in vivo.

  11. Influence of montmorillonite on antimicrobial activity of tetracycline and ciprofloxacin

    Science.gov (United States)

    Lv, Guocheng; Pearce, Cody W.; Gleason, Andrea; Liao, Libing; MacWilliams, Maria P.; Li, Zhaohui

    2013-11-01

    Antibiotics are used not only to fight infections and inhibit bacterial growth, but also as growth promotants in farm livestock. Farm runoff and other farm-linked waste have led to increased antibiotic levels present in the environment, the impact of which is not completely understood. Soil, more specifically clays, that the antibiotic contacts may alter its effectiveness against bacteria. In this study a swelling clay mineral montmorillonite was preloaded with antibiotics tetracycline and ciprofloxacin at varying concentrations and bioassays were conducted to examine whether the antibiotics still inhibited bacterial growth in the presence of montmorillonite. Escherichia coli was incubated with montmorillonite or antibiotic-adsorbed montmorillonite, and then the number of viable bacteria per mL was determined. The antimicrobial activity of tetracycline was affected in the presence of montmorillonite, as the growth of non-resistant bacteria was still found even when extremely high TC doses were used. Conversely, in the presence of montmorillonite, ciprofloxacin did inhibit E. coli bacterial growth at high concentrations. These results suggest that the effectiveness of antimicrobial agents in clayey soils depends on the amount of antibiotic substance present, and on the interactions between the antibiotic and the clays in the soil, as well.

  12. Actividad antimicrobiana de Verbesina encelioides Antimicrobial activity of Verbesina encelioides

    Directory of Open Access Journals (Sweden)

    M.S Toribio

    2005-12-01

    Full Text Available Verbesina encelioides (Cav. Benth. & Hook. (Compuestas es una especie ampliamente distribuida en la Argentina, que se conoce vulgarmente con el nombre de «girasolcito» o «mirasolcito del campo», debido a que presenta flores amarillas en capítulos terminales pedunculados. El objetivo del presente trabajo es evaluar la actividad antimicrobiana de esta especie frente a bacterias Gram positivas, Gram negativas y Candida albicans. Se utilizaron concentraciones crecientes del extracto vegetal para determinar la concentración inhibitoria mínima (CIM mediante el método de dilución en caldo y la concentración bactericida mínima (CBM. Para la determinación de la actividad antimicrobiana, fueron utilizados los siguientes microorganismos: Staphylococcus aureus, S. epidermidis, S. intermedius, Pseudomonas aeruginosa, Streptococcus agalactiae, Salmonella typhimurium, Citrobacter freundii, Proteus spp., Escherichia coli, Candida albicans. Los resultados obtenidos, bajo nuestras condiciones de trabajo, demuestran que el extracto metanólico de los capítulos de Verbesina encelioides presenta actividad antimicrobiana más notoria sobre microorganismos Gram positivos y Candida albicans que contra bacterias Gram negativas, no mostrando actividad contra Citrobacter freundii.Verbesina encelioides (Cav. Benth. & Hook. (Compositae is a species broadly distributed in Argentina commonly known as «girasolcito» or «mirasolcito del cam