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Sample records for cytokine synthesis inhibitory

  1. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein-Barr virus open reading frame BCRFI

    International Nuclear Information System (INIS)

    Vieira, P.; De Waal-Malefyt, R.; Dang, M.N.; Johnson, K.E.; Kastelein, R.; Fiorentino, D.F.; DeVries, J.E.; Roncarolo, M.G.; Mosmann, T.R.; Moore, K.W.

    1991-01-01

    The authors demonstrated the existence of human cytokine synthesis inhibitory factor (DSIF) [interleukin 10 (IL-10)]. cDNA clones encoding human IL-10 (hIL-10) were isolated from a tetanus toxin-specific human T-cell clone. Like mouse IL-10, hIL-10 exhibits strong DNA and amino acid sequence homology to an open reading frame in the Epstein-Barr virus, BDRFL. hIL-10 and the BCRFI product inhibit cytokine synthesis by activated human peripheral blood mononuclear cells and by a mouse Th1 clone. Both hIL-10 and mouse IL-10 sustain the viability of a mouse mast cell line in culture, but BCRFI lacks comparable activity in this way, suggesting that BCRFI may have conserved only a subset of hIL-10 activities

  2. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein-Barr virus open reading frame BCRFI

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, P.; De Waal-Malefyt, R.; Dang, M.N.; Johnson, K.E.; Kastelein, R.; Fiorentino, D.F.; DeVries, J.E.; Roncarolo, M.G.; Mosmann, T.R.; Moore, K.W. (DNAX Research Inst. of Molecular and Cellular Biology, Palo Alto, CA (United States))

    1991-02-15

    The authors demonstrated the existence of human cytokine synthesis inhibitory factor (DSIF) (interleukin 10 (IL-10)). cDNA clones encoding human IL-10 (hIL-10) were isolated from a tetanus toxin-specific human T-cell clone. Like mouse IL-10, hIL-10 exhibits strong DNA and amino acid sequence homology to an open reading frame in the Epstein-Barr virus, BDRFL. hIL-10 and the BCRFI product inhibit cytokine synthesis by activated human peripheral blood mononuclear cells and by a mouse Th1 clone. Both hIL-10 and mouse IL-10 sustain the viability of a mouse mast cell line in culture, but BCRFI lacks comparable activity in this way, suggesting that BCRFI may have conserved only a subset of hIL-10 activities.

  3. Pro-inflammatory cytokine TNF-α is a key inhibitory factor for lactose synthesis pathway in lactating mammary epithelial cells.

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    Kobayashi, Ken; Kuki, Chinatsu; Oyama, Shoko; Kumura, Haruto

    2016-01-15

    Lactose is a milk-specific carbohydrate synthesized by mammary epithelial cells (MECs) in mammary glands during lactation. Lactose synthesis is downregulated under conditions causing inflammation such as mastitis, in which MECs are exposed to high concentrations of inflammatory cytokines. In this study, we investigated whether inflammatory cytokines (TNF-α, IL-1β, and IL-6) directly influence the lactose synthesis pathway by using two types of murine MEC culture models: the monolayer culture of MECs to induce lactogenesis; and the three-dimensional culture of MECs surrounded by Matrigel to induce reconstitution of the alveolar structure in vitro. TNF-α caused severe down-regulation of lactose synthesis-related genes concurrently with the degradation of glucose transporter 1 (GLUT1) from the basolateral membranes in MECs. IL-1β also caused degradation of GLUT1 along with a decrease in the expression level of β-1,4-galactosylransferase 3. IL-6 caused both up-regulation and down-regulation of the expression levels of lactose synthesis-related genes in MECs. These results indicate that TNF-α, IL-1β, and IL-6 have different effects on the lactose synthesis pathway in MECs. Furthermore, TNF-α triggered activation of NFκB and inactivation of STAT5, suggesting that NFκB and STAT5 signaling pathways are involved in the multiple adverse effects of TNF-α on the lactose synthesis pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

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    Leifheit Erica C

    2004-07-01

    Full Text Available Abstract Background The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF has previously been associated with various types of adenocarcinoma. Methods MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA, anti-MIF antibody or MIF anti-sense on cell growth and cytokine expression were analyzed. Results Human bladder cancer cells (HT-1376 secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. Conclusions This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma.

  5. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

    International Nuclear Information System (INIS)

    Meyer-Siegler, Katherine L; Leifheit, Erica C; Vera, Pedro L

    2004-01-01

    The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

  6. Acute myotube protein synthesis regulation by IL-6-related cytokines.

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    Gao, Song; Durstine, J Larry; Koh, Ho-Jin; Carver, Wayne E; Frizzell, Norma; Carson, James A

    2017-11-01

    IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. Copyright © 2017 the

  7. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

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    Shiqi Zhang

    2018-03-01

    Full Text Available Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1, an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c and its target genes, diacylglycerol acyltransferase (DGAT 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL and CGI-58 for adipose triglyceride lipase (ATGL, thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1β, and interleukin 6 (IL-6 induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  8. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

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    Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

    2018-01-01

    Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  9. Inhibitory Effects of Soyeum Pharmacopuncture (SPP on LPS-induced Inflammation Related Cytokine Expressions of RAW 264.7 cells

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    Yoon Mi-Young

    2007-12-01

    Full Text Available Aim : This study was done to investigate whether SPP has inhibitory effects on the activation of RAW 264.7 cells. Method : In tumor necrosis factor-a (TNF-a/ interleukin-1b (IL-1b and IL-6, the mRNA expression of molecular indicators related to inflammatory changes of the Reumatoid Arthritis (RA were examined using quantitative real-time PCR. Results : The treatment of SPP significantly suppressed the expression of proinflammatory cytokines and chemokines such as TNF-a, IL-1b, IL-6 compared with the control. The expression of NOS-II was considerably reduced, which was accompanied by a reduction in the production of nitric oxide (NO. It also reduced the expression of TNF-αin serum of Balb/c mice compared with control group. Conclusion : SPP is an effective herbal material for suppressing the inflammation related cytokines of RAW 264.7 cells.

  10. Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor.

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    Dziedzic, Pawel; Cisneros, José A; Robertson, Michael J; Hare, Alissa A; Danford, Nadia E; Baxter, Richard H G; Jorgensen, William L

    2015-03-04

    Optimization is reported for biaryltriazoles as inhibitors of the tautomerase activity of human macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with numerous inflammatory diseases and cancer. A combined approach was taken featuring organic synthesis, enzymatic assaying, crystallography, and modeling including free-energy perturbation (FEP) calculations. X-ray crystal structures for 3a and 3b bound to MIF are reported and provided a basis for the modeling efforts. The accommodation of the inhibitors in the binding site is striking with multiple hydrogen bonds and aryl-aryl interactions. Additional modeling encouraged pursuit of 5-phenoxyquinolinyl analogues, which led to the very potent compound 3s. Activity was further enhanced by addition of a fluorine atom adjacent to the phenolic hydroxyl group as in 3w, 3z, 3aa, and 3bb to strengthen a key hydrogen bond. It is also shown that physical properties of the compounds can be modulated by variation of solvent-exposed substituents. Several of the compounds are likely the most potent known MIF tautomerase inhibitors; the most active ones are more than 1000-fold more active than the well-studied (R)-ISO-1 and more than 200-fold more active than the chromen-4-one Orita-13.

  11. [Inhibitory effect and mechanism of tofacitinib on the secretion of cytokines by T cells in human peripheral blood].

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    Wu, Kunlun; Zhao, Jun; Wu, Qiongli; Wu, Changyou

    2017-11-01

    Objective To study the inhibitory effect of tofacitinib on the production of cytokines by T cells in human peripheral blood and its mechanism. Methods Peripheral blood mononuclear cells (PBMCs) and purified T cells were cultured and stimulated with anti-CD3 plus anti-CD28 antibodies in the presence or absence of tofacitinib (0.5 μmol/L). The levels of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 2 (IL-2) in the culture supernatants were detected by ELISA, and the expressions of activated molecules CD69 and CD25 on the surface of CD4 + and CD8 + T cells, the production of cytokines and the phosphorylation of signal transducers and transcriptional activators STAT1, STAT3, STAT4 in T cells were examined by flow cytometry. At the same time, the proliferation and apoptosis of T cells were observed by 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE) staining and the flow cy tometry with annexin V-FITC/PI, respectively. Results Tofacitinib inhibited the production of IFN-γ, TNF-α and the expression of CD25 on T cells from the peripheral blood. In addition, the proliferation and the phosphorylation of STAT1, STAT3, STAT4 by T cells were also depressed. However, tofacitinib had no effect on the secretion of IL-2, the expression of CD69 and the apoptosis of T cells. Conclusion Tofacitinib can inhibit the secretion of IFN-γ and TNF-α by T cells in the peripheral blood, and its mechanism might be related to the inhibitory effect of tofacitinib on the activation, proliferation and signal transduction in T cells.

  12. Structure-activity studies of peptidomimetics based on kinase-inhibitory region of suppressors of cytokine signaling 1.

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    La Manna, Sara; Lopez-Sanz, Laura; Leone, Marilisa; Brandi, Paola; Scognamiglio, Pasqualina Liana; Morelli, Giancarlo; Novellino, Ettore; Gomez-Guerrero, Carmen; Marasco, Daniela

    2017-11-20

    Suppressors of Cytokine Signaling (SOCS) proteins are negative regulators of JAK proteins that are receptor-associated tyrosine kinases, which play key roles in the phosphorylation and subsequent activation of several transcription factors named STATs. Unlike the other SOCS proteins, SOCS1 and 3 show, in the N-terminal portion, a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Drug discovery processes of compounds based on KIR sequence demonstrated promising in functional in vitro and in inflammatory animal models and we recently developed a peptidomimetic called PS5, as lead compound. Here, we investigated the cellular ability of PS5 to mimic SOCS1 biological functions in vascular smooth muscle cells and simultaneously we set up a new binding assay for the screening and identification of JAK2 binders based on a SPR experiment that revealed more robust with respect to previous ELISAs. On this basis, we designed several peptidomimetics bearing new structural constraints that were analyzed in both affinities toward JAK2 and conformational features through Circular Dichroism and NMR spectroscopies. Introduced chemical modifications provided an enhancement of serum stabilities of new sequences that could aid the design of future mimetic molecules of SOCS1 as novel anti-inflammatory compounds. © 2017 Wiley Periodicals, Inc.

  13. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

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    Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

    2002-10-01

    The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

  14. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

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    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  15. Evidence for the Involvement of Spinal Cord-Inhibitory and Cytokines-Modulatory Mechanisms in the Anti-Hyperalgesic Effect of Hecogenin Acetate, a Steroidal Sapogenin-Acetylated, in Mice

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    Jullyana S.S. Quintans

    2014-06-01

    Full Text Available Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as ‘sisal’, and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA is a steroidal sapogenin-acetylated that produces antinociceptive activity. Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile. Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p. inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1β. The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms.

  16. In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.

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    Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

    1999-10-01

    Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.

  17. Role of Th-1 cell cytokines, leukemia inhibitory factor and hoxA genes in women with recurrent pregnancy loss

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    Alaa M. Ismail

    2017-12-01

    Conclusion: This study suggests that women with a history of RPL can have abnormal cytokine and gene expression even when not pregnant. Our findings can be a basis for providing of future successful immunological therapy for women with RPL.

  18. Progesterone receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine-induced matrix metalloproteinase 9 activity in vitro.

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    Allen, Terrence K; Feng, Liping; Grotegut, Chad A; Murtha, Amy P

    2014-02-01

    Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.

  19. Inhibitory effects of devil's claw (secondary root of Harpagophytum procumbens) extract and harpagoside on cytokine production in mouse macrophages.

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    Inaba, Kazunori; Murata, Kazuya; Naruto, Shunsuke; Matsuda, Hideaki

    2010-04-01

    Successive oral administration (50 mg/kg) of a 50% ethanolic extract (HP-ext) of devil's claw, the secondary root of Harpagophytum procumbens, showed a significant anti-inflammatory effect in the rat adjuvant-induced chronic arthritis model. HP-ext dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines [interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] in mouse macrophage cells (RAW 264.7). Harpagoside, a major iridoid glycoside present in devil's claw, was found to be one of the active agents in HP-ext and inhibited the production of IL-1beta, IL-6, and TNF-alpha by RAW 264.7.

  20. Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia

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    Park, Hye Young [Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714 (Korea, Republic of); Department of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Nam Deuk [Department of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Gi-Young [Department of Marine Life Sciences, Jeju National University, Jeju 690-756 (Korea, Republic of); Hwang, Hye Jin [Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 (Korea, Republic of); Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714 (Korea, Republic of); Kim, Byung-Woo [Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 (Korea, Republic of); Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714 (Korea, Republic of); Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714 (Korea, Republic of); Kim, Wun Jae [Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Choi, Yung Hyun, E-mail: choiyh@deu.ac.kr [Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-714 (Korea, Republic of); Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan 614-714 (Korea, Republic of); Department of Biomaterial Control, Graduate School, Dongeui University, Busan 614-714 (Korea, Republic of)

    2012-07-15

    Diallyl disulfide (DADS), a main organosulfur component responsible for the diverse biological effects of garlic, displays a wide variety of internal biological activities. However, the cellular and molecular mechanisms underlying DADS' anti-inflammatory activity remain poorly understood. In this study, therefore, the anti-inflammatory effects of DADS were studied to investigate its potential therapeutic effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that pretreatment with DADS prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) in a dose-dependent manner. The inhibition was associated with down-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. DADS also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1) by suppressing the expression of mRNAs for these proteins. The mechanism underlying this protective effect might be related to the inhibition of nuclear factor-kappaB, Akt and mitogen-activated protein kinase signaling pathway activation in LPS-stimulated microglial cells. These findings indicated that DADS is potentially a novel therapeutic candidate for the treatment of various neurodegenerative diseases. -- Highlights: ► DADS attenuates production of NO and PGE2 in LPS-activated BV2 microglia. ► DADS downregulates levels of iNOS and COX-2. ► DADS inhibits production and expression of inflammatory cytokines and chemokine. ► DADS exhibits these effects by suppression of NF-κB, PI3K/Akt and MAPKs pathways.

  1. Nitric oxide-releasing agents enhance cytokine-induced tumor necrosis factor synthesis in human mononuclear cells

    NARCIS (Netherlands)

    Eigler, A; Sinha, B; Endres, S

    1993-01-01

    In septic shock tumor necrosis factor (TNF) leads to increased nitric oxide (NO) production by induction of NO synthase. An inverse regulatory effect, the influence of NO on cytokine synthesis, has rarely been investigated. The present study assessed the influence of NO-releasing agents on TNF

  2. Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells

    International Nuclear Information System (INIS)

    Lee, E.W.; Johnson, J.T.; Garner, C.D.

    1989-01-01

    Effects of endogenously produced and exogenously added benzene metabolites on the nuclear DNA synthetic activity were investigated using a culture system of mouse bone marrow cells. Effects of the metabolites were evaluated by a 30-min incorporation of [ 3 H]thymidine into DNA following a 30-min interaction with the cells in McCoy's 5a medium with 10% fetal calf serum. Phenol and muconic acid did not inhibit nuclear DNA synthesis. However, catechol, 1,2,4-benzenetriol, hydroquinone, and p-benzoquinone were able to inhibit 52, 64, 79, and 98% of the nuclear DNA synthetic activity, respectively, at 24 μM. In a cell-free DNA synthetic system, catechol and hydroquinone did not inhibit the incorporation of [ 3 H]thymidine triphosphate into DNA up to 24 μM but 1,2,4-benzenetriol and p-benzoquinone did. The effect of the latter two benzene metabolites was completely blocked in the presence of 1,4-dithiothreitol (1 mM) in the cell-free assay system. Furthermore, when DNA polymerase α, which requires a sulfhydryl (SH) group as an active site, was replaced by DNA polymerase 1, which does not require an SH group for its catalytic activity, p-benzoquinone and 1,2,4-benzenetriol were unable to inhibit DNA synthesis. Thus, the data imply the p-benzoquinone and 1,2,4-benzenetriol inhibited DNA polymerase α, consequently resulting in inhibition of DNA synthesis in both cellular and cell-free DNA synthetic systems. The present study identifies catechol, hydroquinone, p-benzoquinone, and 1,2,4-benzenetriol as toxic benzene metabolites in bone marrow cells and also suggests that their inhibitory action on DNA synthesis is mediated by mechanism(s) other than that involving DNA damage as a primary cause

  3. Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis-Specific CD4+ T-Cells.

    Directory of Open Access Journals (Sweden)

    Kapil K Saharia

    Full Text Available Little is known about the expression of inhibitory molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4 and programmed-death-1 (PD-1 on Mycobacterium tuberculosis (Mtb-specific CD4 T-cells and how their expression is impacted by TB treatment.Cryopreserved PBMCs from HIV-TB co-infected and TB mono-infected patients with untreated and treated tuberculosis (TB disease were stimulated for six hours with PPD and stained. Using polychromatic flow cytometry, we characterized the differentiation state, cytokine profile, and inhibitory molecule expression on PPD-specific CD4 T-cells.In our HIV-TB co-infected cohort, TB treatment increased the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+IL-2+TNF-α+ and IFN-γ+IL-2+ (p = 0.0004 and p = 0.0002, respectively while decreasing the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+MIP1-β+TNF-α+ and IFN-γ+MIP1-β+. The proportion of PPD-specific CD4 T-cells expressing an effector memory phenotype decreased (63.6% vs 51.6%, p = 0.0015 while the proportion expressing a central memory phenotype increased (7.8% vs. 21.7%, p = 0.001 following TB treatment. TB treatment reduced the proportion of PPD-specific CD4 T-cells expressing CTLA-4 (72.4% vs. 44.3%, p = 0.0005 and PD-1 (34.5% vs. 29.2%, p = 0.03. Similar trends were noted in our TB mono-infected cohort.TB treatment alters the functional profile of Mtb-specific CD4 T-cells reflecting shifts towards a less differentiated maturational profile and decreases PD-1 and CTLA-4 expression. These could serve as markers of reduced mycobacterial burden. Further study is warranted.

  4. Design, synthesis, α-glucosidase inhibitory activity, molecular docking and QSAR studies of benzimidazole derivatives

    Science.gov (United States)

    Dinparast, Leila; Valizadeh, Hassan; Bahadori, Mir Babak; Soltani, Somaieh; Asghari, Behvar; Rashidi, Mohammad-Reza

    2016-06-01

    In this study the green, one-pot, solvent-free and selective synthesis of benzimidazole derivatives is reported. The reactions were catalyzed by ZnO/MgO containing ZnO nanoparticles as a highly effective, non-toxic and environmentally friendly catalyst. The structure of synthesized benzimidazoles was characterized using spectroscopic technics (FT-IR, 1HNMR, 13CNMR). Synthesized compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 3c, 3e, 3l and 4n were potent inhibitors with IC50 values ranging from 60.7 to 168.4 μM. In silico studies were performed to explore the binding modes and interactions between enzyme and synthesized benzimidazoles. Developed linear QSAR model based on density and molecular weight could predict bioactivity of newly synthesized compounds well. Molecular docking studies revealed the availability of some hydrophobic interactions. In addition, the bioactivity of most potent compounds had good correlation with estimated free energy of binding (ΔGbinding) which was calculated according to docked best conformations.

  5. Peripheral Injection of SB203580 Inhibits the Inflammatory-Dependent Synthesis of Proinflammatory Cytokines in the Hypothalamus

    Directory of Open Access Journals (Sweden)

    Andrzej P. Herman

    2014-01-01

    Full Text Available The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL- 1β, IL-6, and tumor necrosis factor (TNF α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS (400 ng/kg over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK, which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P<0.01 synthesis of IL-1β and reduced (P<0.01 the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P<0.01 gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P<0.01 LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

  6. Changing of expression level of fas-antigen (CD95), cytokines synthesis and production after irradiation in low doses

    International Nuclear Information System (INIS)

    Kalinina, N.M.; Solntceva, O.S.; Bytchkova, N.V.; Nikiforov, A.M.

    1997-01-01

    It is known that bone marrow progenitor (CD34+), tymocytes and peripheral blood lymphocytes (PBL) are most radiosensitive than other cell types. Even low doses of radiation induce apoptosis. The investigators suggest that it is possible relationship between synthesis and production of cytokines and apoptotic process. With the purpose to determine correlation between expression of Fas-antigen and synthesis of cytokines after low doses irradiation the experiments by irradiation PBL of healthy persons in vitro were held. Cells were X-irradiated by 12,5, 25 and 50 cGy. In consequence of the experiments increasing of Fas-antigen was revealed. This increasing correlated with changing in synthesis and production of cytokines. Also the Chernobyl's accident liquidators (CAL) were investigated. After comparison data in the group CAL (I) with data in the control group (II) increasing of Fas-antigen expression was revealed. Also in I group was discovered increasing of the cell number sinthesied interleukine-4 (IL-4) and interleukine-6 (IL-6). Interleukine-lβ (IL-1 β) producing pell were decreased. These changes have been correlated with degree of immunodeficiency at CAL. These data allow to consider the apoptosis as cell mechanism included in pathogenesis of diseases, which can be showed later long time after irradiation. (author)

  7. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  8. Association of macrophage inhibitory cytokine-1 with nutritional status, body composition and bone mineral density in patients with anorexia nervosa: the influence of partial realimentation.

    Science.gov (United States)

    Dostálová, Ivana; Kaválková, Petra; Papežová, Hana; Domluvilová, Daniela; Zikán, Vít; Haluzík, Martin

    2010-04-23

    Macrophage inhibitory cytokine-1 (MIC-1) is a key inducer of cancer-related anorexia and weight loss. However, its possible role in the etiopathogenesis of nutritional disorders of other etiology such as anorexia nervosa (AN) is currently unknown. We measured fasting serum concentrations of MIC-1 in patients with AN before and after 2-month nutritional treatment and explored its relationship with nutritional status, metabolic and biochemical parameters. Sixteen previously untreated women with AN and twenty-five normal-weight age-matched control women participated in the study. We measured serum concentrations of MIC-1 and leptin by ELISA, free fatty acids by enzymatic colorimetric assay, and biochemical parameters by standard laboratory methods; determined resting energy expenditure by indirect calorimetry; and assessed bone mineral density and body fat content by dual-energy X-ray absorptiometry. ANOVA, unpaired t-test or Mann-Whitney test were used for groups comparison as appropriate. The comparisons of serum MIC-1 levels and other studied parameters in patients with AN before and after partial realimentation were assessed by paired t-test or Wilcoxon Signed Rank Test as appropriate. At baseline, fasting serum MIC-1 concentrations were significantly higher in patients with AN relative to controls. Partial realimentation significantly reduced serum MIC-1 concentrations in patients with AN but it still remained significantly higher compared to control group. In AN group, serum MIC-1 was inversely related to Buzby nutritional risk index, serum insulin-like growth factor-1, serum glucose, serum total protein, serum albumin, and lumbar bone mineral density and it significantly positively correlated with the duration of AN and age. MIC-1 concentrations in AN patients are significantly higher relative to healthy women. Partial realimentation significantly decreased MIC-1 concentration in AN group. Clinical significance of these findings needs to be further clarified.

  9. Association of macrophage inhibitory cytokine-1 with nutritional status, body composition and bone mineral density in patients with anorexia nervosa: the influence of partial realimentation

    Directory of Open Access Journals (Sweden)

    Zikán Vít

    2010-04-01

    Full Text Available Abstract Background Macrophage inhibitory cytokine-1 (MIC-1 is a key inducer of cancer-related anorexia and weight loss. However, its possible role in the etiopathogenesis of nutritional disorders of other etiology such as anorexia nervosa (AN is currently unknown. Methods We measured fasting serum concentrations of MIC-1 in patients with AN before and after 2-month nutritional treatment and explored its relationship with nutritional status, metabolic and biochemical parameters. Sixteen previously untreated women with AN and twenty-five normal-weight age-matched control women participated in the study. We measured serum concentrations of MIC-1 and leptin by ELISA, free fatty acids by enzymatic colorimetric assay, and biochemical parameters by standard laboratory methods; determined resting energy expenditure by indirect calorimetry; and assessed bone mineral density and body fat content by dual-energy X-ray absorptiometry. ANOVA, unpaired t-test or Mann-Whitney test were used for groups comparison as appropriate. The comparisons of serum MIC-1 levels and other studied parameters in patients with AN before and after partial realimentation were assessed by paired t-test or Wilcoxon Signed Rank Test as appropriate. Results At baseline, fasting serum MIC-1 concentrations were significantly higher in patients with AN relative to controls. Partial realimentation significantly reduced serum MIC-1 concentrations in patients with AN but it still remained significantly higher compared to control group. In AN group, serum MIC-1 was inversely related to Buzby nutritional risk index, serum insulin-like growth factor-1, serum glucose, serum total protein, serum albumin, and lumbar bone mineral density and it significantly positively correlated with the duration of AN and age. Conclusions MIC-1 concentrations in AN patients are significantly higher relative to healthy women. Partial realimentation significantly decreased MIC-1 concentration in AN group

  10. Studies on the biosynthesis of macrophage migration inhibitory factor in delayed hypersensitivity, 1. Effects of inhibitors of nucleic acid and protein synthesis on the production of macrophage migration inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Y; Yamamoto, S; Morisawa, S [Osaka City Univ. (Japan). Faculty of Medicine

    1973-03-01

    Specific antigenic stimulation of sensitized lymphocytes leads to the production of macrophage migration inhibitory factor (MIF). Production of MIF is inhibited by mitomycin C, actinomycin D, and puromycin. These inhibition effects are studied by using thymidine-/sup 3/H. The first two of these antibiotics only inhibit MIF production when added to the culture medium at a very early stage of antigenic stimulation. In contrast, puromycin exerts its inhibitory effect several hours after the antigenic stimulation, but not at an earlier stage. MIF behaves like a protein, so it seems likely that synthesis of RNA is necessary for MIF formation and MIF synthesis may start as early as a few hours after specific antigenic activation of the sensitized lymphocytes. The inhibitory effects of the antibiotics are discussed in relation to the kinetics of MIF production.

  11. Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.

    Science.gov (United States)

    Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong

    2018-04-01

    Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.

  12. Novel green synthesis of gold nanoparticles using Citrullus lanatus rind and investigation of proteasome inhibitory activity, antibacterial, and antioxidant potential

    Science.gov (United States)

    Patra, Jayanta Kumar; Baek, Kwang-Hyun

    2015-01-01

    Biological synthesis of nanoparticles using nontoxic, eco-friendly approaches is gaining importance owing to their fascinating biocompatibility and environmentally benign nature. This study describes the green synthesis approach for synthesis of gold nanoparticles (ANPs) using aqueous extract of the rind of watermelon as a fruit waste and evaluate its biopotential in terms of proteasome inhibitory activity, antibacterial, and antioxidant potential. The synthesized ANPs were characterized using UV–vis spectroscopy, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The surface plasmon resonance spectra of ANPs were obtained at 560 nm. Scanning electron microscopy image revealed that particles had a spherical shape and have a size distribution of 20–140 nm, followed by the elemental analysis by energy-dispersive X-ray spectroscopy. X-ray diffraction analysis confirmed the crystallite nature of the ANPs and Fourier-transform infrared spectroscopy revealed the involvement of bioactive compounds from watermelon rind in the synthesis, capping, and stabilization of ANPs. ANPs exhibited potential antibacterial activity against five different foodborne pathogenic bacteria with diameter of inhibition zones ranged between 9.23 and 11.58 mm. They also displayed strong synergistic antibacterial activity together with kanamycin (11.93–21.08 mm inhibition zones) and rifampicin (10.32–24.84 mm inhibition zones). ANPs displayed strong antioxidant activity in terms of DPPH radical scavenging (24.69%), nitric oxide scavenging (25.62%), ABTS scavenging (29.42%), and reducing power. Significantly high proteasome inhibitory potential of the ANPs (28.16%) could be highly useful for cancer treatment and targeted cancer drug delivery. Overall, results highlight a potential low-cost green method of synthesizing ANPs from food waste materials. Significant biopotentials of synthesized ANPs could make it a potential

  13. Isolation of proanthocyanidins from red wine, and their inhibitory effects on melanin synthesis in vitro.

    Science.gov (United States)

    Fujimaki, Takahiro; Mori, Shoko; Horikawa, Manabu; Fukui, Yuko

    2018-05-15

    The red wines made from Vitis vinifera were identified as skin-whitening effectors by using in vitro assays. OPCs in the wine were evaluated for tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers, upper and middle units joined with 4 → 8 bonds, showed stronger effects compared to trimers with 4 → 6 linkages. Interestingly, (-)-epicatechin-(4β → 8)-(-)-epicatechin 3-O-gallate, which is a unique component of grapes has potent inhibitory effects on both tyrosinase and melanogenesis. Our data provide structural information about such active compounds. These results suggest that red wines containing OPC, have high melanogenesis inhibitory effect and are supposed to have skin-whitening effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Potent inhibitory effects of D-tagatose on the acid production and water-insoluble glucan synthesis of Streptococcus mutans GS5 in the presence of sucrose.

    Science.gov (United States)

    Sawada, Daijo; Ogawa, Takaaki; Miyake, Minoru; Hasui, Yoshinori; Yamaguchi, Fuminori; Izumori, Ken; Tokuda, Masaaki

    2015-01-01

    We examined and compared the inhibitory effects of D-tagatose on the growth, acid production, and water-insoluble glucan synthesis of GS5, a bacterial strain of Streptococcus mutans, with those of xylitol, D-psicose, L-psicose and L-tagatose. GS5 was cultured for 12h in a medium containing 10% (w/v) of xylitol, D-psicose, L-psicose, D-tagatose or L-tagatose, and the inhibitory effect of GS5 growth was assessed. Each sugar showed different inhibitory effects on GS5. Both D-tagatose and xylitol significantly inhibited the acid production and water-insoluble glucan synthesis of GS5 in the presence of 1% (w/v) sucrose. However, the inhibitory effect of acid production by D-tagatose was significantly stronger than that of xylitol in presence of sucrose.

  15. Potent Inhibitory Effects of D-tagatose on the Acid Production and Water-insoluble Glucan Synthesis of Streptococcus mutans GS5 in the Presence of Sucrose

    OpenAIRE

    Sawada, Daijo; Ogawa, Takaaki; Miyake, Minoru; Hasui, Yoshinori; Yamaguchi, Fuminori; Izumori, Ken; Tokuda, Masaaki

    2015-01-01

    We examined and compared the inhibitory effects of D-tagatose on the growth, acid production, and water-insoluble glucan synthesis of GS5, a bacterial strain of Streptococcus mutans, with those of xylitol, D-psicose, L-psicose and L-tagatose. GS5 was cultured for 12h in a medium containing 10オ (w/v) of xylitol, D-psicose, L-psicose, D-tagatose or L-tagatose, and the inhibitory effect of GS5 growth was assessed. Each sugar showed different inhibitory effects on GS5. Both D-tagatose and xylitol...

  16. Novel green synthesis of gold nanoparticles using Citrullus lanatus rind and investigation of proteasome inhibitory activity, antibacterial, and antioxidant potential

    Directory of Open Access Journals (Sweden)

    Patra JK

    2015-12-01

    Full Text Available Jayanta Kumar Patra, Kwang-Hyun Baek School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk, Republic of Korea Abstract: Biological synthesis of nanoparticles using nontoxic, eco-friendly approaches is gaining importance owing to their fascinating biocompatibility and environmentally benign nature. This study describes the green synthesis approach for synthesis of gold nanoparticles (ANPs using aqueous extract of the rind of watermelon as a fruit waste and evaluate its biopotential in terms of proteasome inhibitory activity, antibacterial, and antioxidant potential. The synthesized ANPs were characterized using UV–vis spectroscopy, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The surface plasmon resonance spectra of ANPs were obtained at 560 nm. Scanning electron microscopy image revealed that particles had a spherical shape and have a size distribution of 20–140 nm, followed by the elemental analysis by energy-dispersive X-ray spectroscopy. X-ray diffraction analysis confirmed the crystallite nature of the ANPs and Fourier-transform infrared spectroscopy revealed the involvement of bioactive compounds from watermelon rind in the synthesis, capping, and stabilization of ANPs. ANPs exhibited potential antibacterial activity against five different foodborne pathogenic bacteria with diameter of inhibition zones ranged between 9.23 and 11.58 mm. They also displayed strong synergistic antibacterial activity together with kanamycin (11.93–21.08 mm inhibition zones and rifampicin (10.32–24.84 mm inhibition zones. ANPs displayed strong antioxidant activity in terms of DPPH radical scavenging (24.69%, nitric oxide scavenging (25.62%, ABTS scavenging (29.42%, and reducing power. Significantly high proteasome inhibitory potential of the ANPs (28.16% could be highly useful for cancer treatment and targeted cancer drug delivery. Overall, results highlight a

  17. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    OpenAIRE

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Ro, Hyunju; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in ? -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respect...

  18. Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells.

    Science.gov (United States)

    Bommer, I; Muzzio, D O; Zygmunt, M; Jensen, F

    2016-08-01

    The main message of this work is the fact that female sex hormones, progesterone and estradiol, whose levels significantly rise during pregnancy, inhibit the production of anti-inflammatory cytokine IL-10 with no apparent effect on pro-inflammatory cytokine TNF-α by activated MZ B cells. This is an important piece of information and helps to better understand how the maternal immune system controls the balance between immune tolerance and immune activation during pregnancy leading to the simultaneously acceptance of the semi-allogeneic fetus and the proper defense of the mother against pathogens during this critical period of time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives.

    Science.gov (United States)

    Taha, Muhammad; Tariq Javid, Muhammad; Imran, Syahrul; Selvaraj, Manikandan; Chigurupati, Sridevi; Ullah, Hayat; Rahim, Fazal; Khan, Fahad; Islam Mohammad, Jahidul; Mohammed Khan, Khalid

    2017-10-01

    α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1 HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC 50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC 50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Opposite cytokine synthesis by fibroblasts in contact co-culture with osteosarcoma cells compared with transwell co-cultures.

    Science.gov (United States)

    David, Manu S; Kelly, Elizabeth; Zoellner, Hans

    2013-04-01

    We recently reported exchange of membrane and cytoplasm during contact co-culture between human Gingival Fibroblasts (h-GF) and SAOS-2 osteosarcoma cells, a process we termed 'cellular sipping' to reflect the manner in which cells become morphologically diverse through uptake of material from the opposing cell type, independent of genetic change. Cellular sipping is increased by Tumor Necrosis Factor-α (TNF-α), and we here show for the first time altered cytokine synthesis in contact co-culture supporting cellular sipping compared with co-culture where h-GF and SAOS-2 were separated in transwells. SAOS-2 had often undetectably low cytokine levels, while Interleukin-6 (IL-6), Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) were secreted primarily by TNF-α stimulated h-GF and basic Fibroblast Growth Factor (FGF) was prominent in h-GF lysates (p cultures permitting cellular sipping had lower IL-6, G-CSF and GM-CSF levels, as well as higher lysate FGF levels compared with TNF-α treated h-GF alone (p cultures in transwells, with increased IL-6, G-CSF and GM-CSF levels (p cultures where cellular sipping occurs, potentially contributing to tumor inflammatory responses. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  1. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

    Directory of Open Access Journals (Sweden)

    Chunyu Liu

    2016-08-01

    Full Text Available Aflatoxin B1 (AFB1 is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed and AFB1 group (0.6 mg pure AFB1/kg feed. At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+ by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers.

  2. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

    Energy Technology Data Exchange (ETDEWEB)

    Liu, C.; Jiang, M.; Fang, J.; Peng, X.; Cui, H.

    2016-11-01

    Afatoxin B1 (AFB1) is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed) and AFB1 group (0.6 mg pure AFB1/kg feed). At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α) mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+) by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers. (Author)

  3. Role of the Leukemia-Inhibitory Factor Gene Mutations in Infertile Women:The Embryo-Endometrial Cytokine Cross Talk during Implantation-a Delicate Homeostatic Equilibrium

    Czech Academy of Sciences Publication Activity Database

    Králíčková, M.; Šíma, Petr; Rokyta, Z.

    2005-01-01

    Roč. 50, č. 3 (2005), s. 179-186 ISSN 0015-5632 R&D Projects: GA ČR GA301/02/1232; GA ČR GA301/05/0078 Institutional research plan: CEZ:AV0Z50200510 Keywords : leukemia inhibitory factor * interleukin 11 Subject RIV: EE - Microbiology, Virology Impact factor: 0.918, year: 2005

  4. A synthesis of evidence on inhibitory control and auditory hallucinations based on the Research Domain Criteria (RDoC framework.

    Directory of Open Access Journals (Sweden)

    Johanna C. Badcock

    2014-03-01

    Full Text Available The National Institute of Mental Health initiative called the Research Domain Criteria (RDoC project aims to provide a new approach to understanding mental illness grounded in the fundamental domains of human behaviour and psychological functioning. To this end the RDoC framework encourages researchers and clinicians to think outside the [diagnostic]box, by studying symptoms, behaviours or biomarkers that cut across traditional mental illness categories. In this article we examine and discuss how the RDoC framework can improve our understanding of psychopathology by zeroing in on hallucinations- now widely recognized as a symptom that occurs in a range of clinical and non-clinical groups. We focus on a single domain of functioning - namely cognitive [inhibitory] control - and assimilate key findings structured around the basic RDoC units of analysis, which span the range from observable behaviour to molecular genetics. Our synthesis and critique of the literature provides a deeper understanding of the mechanisms involved in the emergence of auditory hallucinations, linked to the individual dynamics of inhibitory development before and after puberty; favours separate developmental trajectories for clinical and nonclinical hallucinations; yields new insights into co-occurring emotional and behavioural problems; and suggests some novel avenues for treatment.

  5. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  6. Biochemical Evidence of L-Dopa Synthesis in a Cytokine-Resilient Aspergillus oryzae

    International Nuclear Information System (INIS)

    Ali, S.; Saleem, R.

    2016-01-01

    The present work describes the microbiological production of 3,4 dihydroxy-L-phenylalanine (L-dopa) from a cytokine-inhibited mold culture of Aspergillus oryzae (strain Ck-R6). A level of 15 μg/ml cytokine was found optimal for culture resistance and better dopa-dopamine activity. Synthetic L-tyrosine was used as a basal carbon source. The aerobic reactions were carried out using pre-grown mycelia as a direct tyrosinase source. The mycelia were cultivated using 200 ml of GPY mineral-salt medium and developed at 30 degree C for 48 h (240 rpm) in 500 ml Erlenmeyer flasks. L-dopa production was found optimal when L-ascorbic acid (5 mg/ml) was added 6 min after starting the reaction (120 rpm). The maximal production (2.2 mg/ml L-dopa) was obtained when L-tyrosine concentration was 2.5 mg/ml. Mycelial level (75 mg/ml) and time of reaction (40 min) were also evaluated. L-Tyrosine consumption was found to be 2.1 mg/ml. After optimizing the reaction conditions, particularly L-ascorbic acid addition, a 30 percent improved L-dopa yield was achieved compared to control when the parameters including time of reaction (40 min), L-tyrosine concentration (2.5 mg/ml) and temperature (50 degree C) were optimized by two-factorial Plackett-Burman design (PBD). (author)

  7. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    Science.gov (United States)

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content. PMID:23781272

  8. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    Directory of Open Access Journals (Sweden)

    Hwayong Park

    2013-01-01

    Full Text Available To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

  9. Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin-Based Design and Synthesis.

    Science.gov (United States)

    Badavath, Vishnu N; Baysal, İpek; Uçar, Gülberk; Mondal, Susanta K; Sinha, Barij N; Jayaprakash, Venkatesan

    2016-01-01

    Ferulic acid has structural similarity with curcumin which is being reported for its monoamine oxidase (MAO) inhibitory activity. Based on this similarity, we designed a series of ferulic acid amides 6a-m and tested for their inhibitory activity on human MAO (hMAO) isoforms. All the compounds were found to inhibit the hMAO isoforms either selectively or non-selectively. Nine compounds (6a, 6b, 6g-m) were found to inhibit hMAO-B selectively, whereas the other four (6c-f) were found to be non-selective. There is a gradual shift from hMAO-B selectivity (6a,b) to non-selectivity (6c-f) as there is an increase in chain length at the amino terminus. In case of compounds having an aromatic nucleus at the amino terminus, increasing the carbon number between N and the aromatic ring increases the potency as well as selectivity toward hMAO-B. Compounds 6f, 6j, and 6k were subjected to membrane permeability and metabolic stability studies by in vitro assay methods. They were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline. In order to understand the structural features responsible for the potency and selectivity of 6k, we carried out a molecular docking simulation study. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on mushroom tyrosinase.

    Science.gov (United States)

    Tokiwa, Y; Kitagawa, M; Raku, T

    2007-03-01

    A novel tyrosinase inhibitor, an arbutin derivative having undecylenic acid at the 6-position of its glucose moiety, was enzymatically synthesized. Its inhibitory activity was studied in vitro by using catechol and phenol as substrates. The IC(50) value of the arbutin ester on tyrosinase using catechol (4 x 10(-4) M) was 1% of that when arbutin (4 x 10(-2) M) was used. Using phenol, IC(50) of the arbutin ester (3 x 10(-4) M) as substrate was 10% of that of arbutin (3 x 10(-3) M). These results suggest that the arbutin ester inhibits the latter part of the tyrosinase reaction, which consists of hydroxylation and oxidation.

  11. Synthesis and GGCT Inhibitory Activity of N-Glutaryl-L-alanine Analogues.

    Science.gov (United States)

    Ii, Hiromi; Yoshiki, Tatsuhiro; Hoshiya, Naoyuki; Uenishi, Jun'ichi

    2016-01-01

    γ-Glutamylcyclotransferase (GGCT) is an important enzyme that cleaves γ-glutamyl-amino acid in the γ-glutamyl cycle to release 5-oxoproline and amino acid. Eighteen N-acyl-L-alanine analogues including eleven new compounds have been synthesized and examined for their inhibitory activity against recombinant human GGCT protein. Simple N-glutaryl-L-alanine was found to be the most potent inhibitor for GGCT. Other N-glutaryl-L-alanine analogues having methyl and dimethyl substituents at the 2-position were moderately effective, while N-(3R-aminoglutary)-L-alanine, the substrate having an (R)-amino group at the 3-position or N-(N-methyl-3-azaglutaryl)-L-alanine, the substrate having an N-methyl substituent on the 3-azaglutaryl carbon, in constract, exhibited excellent inhibition properties.

  12. Enhanced Inhibitory Effect of Ultra-Fine Granules of Red Ginseng on LPS-induced Cytokine Expression in the Monocyte-Derived Macrophage THP-1 Cells

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    Hong-Yeoul Kim

    2008-08-01

    Full Text Available Red ginseng is one of the most popular traditional medicines in Korea because its soluble hot-water extract is known to be very effective on enhancing immunity as well as inhibiting inflammation. Recently, we developed a new technique, called the HACgearshift system, which can pulverize red ginseng into the ultra-fine granules ranging from 0.2 to 7.0 μm in size. In this study, the soluble hot-water extract of those ultra-fine granules of red ginseng (URG was investigated and compared to that of the normal-sized granules of red ginseng (RG. The high pressure liquid chromatographic analyses of the soluble hot-water extracts of both URG and RG revealed that URG had about 2-fold higher amounts of the ginsenosides, the biologically active components in red ginseng, than RG did. Using quantitative RT-PCR, cytokine profiling against the Escherichia coli lipopolysaccharide (LPS in the monocyte-derived macrophage THP-1 cells demonstrated that the URG-treated cells showed a significant reduction in cytokine expression than the RG-treated ones. Transcription expression of the LPS-induced cytokines such as TNF-α, IL-1β, IL-6, IL-8, IL-10, and TGF-β was significantly inhibited by URG compared to RG. These results suggest that some biologically active and soluble components in red ginseng can be more effectively extracted from URG than RG by standard hot-water extraction.

  13. Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease Inhibitory Assay.

    Science.gov (United States)

    Nisar, Muhammad; Khan, Shujaat Ali; Qayum, Mughal; Khan, Ajmal; Farooq, Umar; Jaafar, Hawa Z E; Zia-Ul-Haq, Muhammad; Ali, Rashid

    2016-03-25

    The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH₄ as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl) solution, and heat. Capping with metal ions (Ag/Au-cip) has significant implications for the solubility, pharmacokinetics and bioavailability of fluoroquinolone molecules. The metallic nanoparticles were characterized by several techniques such as ultraviolet visible spectroscopy (UV), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The nanoparticles synthesized using silver and gold were subjected to energy dispersive X-ray tests in order to show their metallic composition. The NH moiety of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic studies. The synthesized nanoparticles were also assessed for urease inhibition potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease enzyme inhibitory potential, with IC50 = 1.181 ± 0.02 µg/mL and 52.55 ± 2.3 µg/mL, compared to ciprofloxacin (IC50 = 82.95 ± 1.62 µg/mL). MNPs also exhibited significant antibacterial activity against selected bacterial strains.

  14. Synthesis, structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases.

    Science.gov (United States)

    Jing, Changling; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Qu, Dan; Niu, Fang; Zhu, Hailiang; You, Zhonglu

    2016-01-15

    A series of new cobalt(III) complexes were prepared. They are [CoL(1)(py)3]·NO3 (1), [CoL(2)(bipy)(N3)]·CH3OH (2), [CoL(3)(HL(3))(N3)]·NO3 (3), and [CoL(4)(MeOH)(N3)] (4), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N'-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N'-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC50 values of 4.27 and 0.35 μmol L(-1), respectively. Complex 2 has medium activity against urease, with IC50 value of 68.7 μmol L(-1). While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects.

    Science.gov (United States)

    Gul, Halise Inci; Kucukoglu, Kaan; Yamali, Cem; Bilginer, Sinan; Yuca, Hafize; Ozturk, Iknur; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T

    2016-08-01

    In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by (1)H NMR, (13)CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1-S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1-S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with Kis in the range of 1.79 ± 0.22-2.73 ± 0.08 nM against hCA I and in the range of 1.72 ± 0.58-11.64 ± 5.21 nM against hCA II, respectively.

  16. Synthesis and evaluation of 2-benzylidene-1-tetralone derivatives for monoamine oxidase inhibitory activity.

    Science.gov (United States)

    Amakali, Klaudia T; Legoabe, Lesetja Jan; Petzer, Anel; Petzer, Jacobus P

    2018-05-01

    Chalcone has been identified as a promising lead for the design of monoamine oxidase (MAO) inhibitors. This study attempted to discover potent and selective chalcone-derived MAO inhibitors by synthesising a series consisting of various cyclic chalcone derivatives. The cyclic chalcones were selected based on the possibility that their restricted structures would confer a higher degree of MAO isoform selectivity, and included the following chemical classes: 1-indanone, 1-tetralone, 1-benzosuberone, chromone, thiochromone, 4-chromanone and 4-thiochromanone. The results showed that the cyclic chalcones are in general good potency, and in most instances specific inhibitors of the human MAO-B isoform. Among these compounds, the 4-chromanone derivative was the most potent MAO-B inhibitor with an IC50 value of 0.156 µM. To further investigate the MAO inhibition of cyclic chalcones, a series of twenty-three 2-benzylidene-1-tetralone derivatives were synthesised and evaluated as MAO inhibitors. Most 2-benzylidene-1-tetralones possess good inhibitory activity and specificity for MAO-B with the most potent inhibitor displaying an IC50 value of 0.0064 µM, while the most potent MAO-A inhibitor possessed an IC50 value of 0.754 µM. This study thus shows that certain cyclic chalcones are human MAO-B inhibitors, compounds that could be suitable for the treatment of neurodegenerative disorders such as Parkinson's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Uterine Msx-1 and Wnt4 signaling becomes aberrant in mice with the loss of leukemia inhibitory factor or Hoxa-10: evidence for a novel cytokine-homeobox-Wnt signaling in implantation.

    Science.gov (United States)

    Daikoku, Takiko; Song, Haengseok; Guo, Yong; Riesewijk, Anne; Mosselman, Sietse; Das, Sanjoy K; Dey, Sudhansu K

    2004-05-01

    Successful implantation absolutely depends on the reciprocal interaction between the implantation-competent blastocyst and the receptive uterus. Expression and gene targeting studies have shown that leukemia inhibitory factor (LIF), a cytokine of the IL-6 family, and Hoxa-10, an abdominalB-like homeobox gene, are crucial to implantation and decidualization in mice. Using these mutant mice, we sought to determine the importance of Msx-1 (another homeobox gene formerly known as Hox-7.1) and of Wnt4 (a ligand of the Wnt family) signaling in implantation because of their reported functions during development. We observed that Msx-1, Wnt4, and a Wnt antagonist sFRP4 are differentially expressed in the mouse uterus during the periimplantation period, suggesting their role in implantation. In addition, we observed an aberrant uterine expression of Msx-1 and sFRP4 in Lif mutant mice, and of Wnt4 and sFRP4 in Hoxa-10 mutant mice, further reinforcing the importance of these signaling pathways in implantation. Collectively, the present results provide evidence for a novel cytokine-homeotic-Wnt signaling network in implantation.

  18. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro

    International Nuclear Information System (INIS)

    Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.

    1987-01-01

    The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone

  19. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-α both in vitro and in vivo systems

    Science.gov (United States)

    Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

    2009-01-01

    Background Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-α in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. Methods The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-α and oleic acid treated cells was evaluated using flow cytometry. PPAR-γ translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Results Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-α inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-α and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Conclusion

  20. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.

    Science.gov (United States)

    Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

    2009-06-26

    Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Oleic acid was found to

  1. IMPACT OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C ON CYTOKINE SYNTHESIS AND HEPATIC FIBROSING PROCESSES

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    V. V. Shchekotov

    2015-01-01

    Full Text Available Objective: to estimate the time course of changes in the levels of tumor necrosis factor-α (TNF-α, interleukin-4 (IL-4, IL-6, and the hepatic fibrosis indicators hyaluronic acid (HA and liver elasticity index during combined antiviral therapy (AVT with interferon alpha-2b and ribavirin in patients with chronic hepatitis C (CHC. Subjects and methods. Fifty patients with CHC were examined. Serum TNF-α, IL-6, IL-4, and HA were estimated using an enzyme immunoassay. The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of AVT. A virological response was monitored at therapy completion and 6 months later. Results. The patients with CHC in the reactivation phase were found to have enhanced TNF-α, IL-6, and IL-4 activities in 84, 60, and 100 % of the cases, respectively (р < 0.001, р = 0.01, р < 0.001, respectively. The median serum concentration of HA in CHC was 1.8-fold higher than that in the control group (p = 0.03; the liver elastic index averaged 6.5 kPa. TNF-α and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators. At combined AVT completion, the virological response rate was as high as 85 %, which was attended by a considerable reduction in cytolysis, HA concentrations, and liver density index to 5.4 kPa (3.6–6.8 kPa (p < 0.04, and in the activity of the examined cytokines. The sustained virological response rate was 80 %. Only IL-4 levels decreased and TNF-α and IL-6 concentration remained at the baseline level in patients unresponsive to AVT. Conclusion. It is expedient to monitor TNF-α, IL-4, IL-6, and HA to evaluate the severity of liver involvement in CHC and to predict the efficiency of AVT.

  2. Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation.

    Science.gov (United States)

    Fei, Xiang; Je, In-Gyu; Shin, Tae-Yong; Kim, Sang-Hyun; Seo, Seung-Yong

    2017-05-29

    Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing ( S )-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several ( S )- and ( R )-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

  3. REGULATION OF TLR/RLR GENE ACTIVITY AND SYNTHESIS OF CYTOKINES DURING PHORBOL MYRISTATE ACETATE (PMA-INDUCED DIFFERENTIATION OF THP-1 MONOCYTES INTO MACROPHAGE-LIKE CELLS

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2017-01-01

    Full Text Available The levels of TLR/RLR gene expression and production of some cytokines were studied in monocytic THP-1 cell line during its differentiation to mature macrophage-like forms induced by phorbol 12-myristate 13-acetate (PMA treatment for 1 and 5 days in vitro. For the first time, we have shown high induction levels for the genes that encode signaling immune receptors and transcription factors in response to PMA, as well as inhibitory effects of TLR3, TLR7/TLR8, TLR9-agonists in mature macrophages. The PMAactivated THP-1 macrophage-like cells secreted large quantitities of inflammatory IL-1β and TNFα cytokines into culture medium.

  4. THE CYTOKINES SYNTHESIS IN VITRO IN THE TICK-BORNE ENCEPHALITIS VIRUS INFECTED CELLS AND IN THE PRESENCE OF INACTIVATED VACCINE

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    M. V. Mesentseva

    2014-01-01

    Full Text Available Abstract. Tick-borne encephalitis (TBE is severe neuroinfectious disease with involvement of immune mechanisms in pathogenesis. Comparative analysis of synthesis of key cytokines had been performed for the TBE virus (TBEV infected cells and in the presence of inactivated vaccine against TBE in vitro. Persistent TBEV infection of immortal tissue culture of human larynx cancer cells caused transcription activation of interferons IFNα, IFNγ, IFNλ1, interleukins IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, tumour necrosis factor TNFα as well as one of apoptosis factors Fas. Comparison of transcription and production of cytokines revealed that the TBEV infection resulted in posttranscription Th1 shift of cytokine response. In the presence of inactivated vaccine against TBE based on the same strain Sofjin of the TBEV activation of transcription of cytokines IFNα, IFNλ1, IL-4, IL-10 was also observed as after the TBEV infection that together with an additional stimulation of GM-CSF production might serve as an evidence of Th2 response. Involvement of IFNIII type (IFNλ1 both during persistent infection and after addition of inactivated vaccines was found in the first time. Differences in dynamics of cytokines IL-2, IL-8, IL-10, IL-12, TNFα response during the TBEV infection and in the presence of inactivated vaccine are described.

  5. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  6. Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils.

    Science.gov (United States)

    Higa, Shinji; Hirano, Toru; Kotani, Mayumi; Matsumoto, Motonobu; Fujita, Akihito; Suemura, Masaki; Kawase, Ichiro; Tanaka, Toshio

    2003-06-01

    Activation of mast cells and basophils through allergen stimulation releases chemical mediators and synthesizes cytokines. Among these cytokines, IL-4, IL-13, and IL-5 have major roles in allergic inflammation. We sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) for the inhibition of cytokine expression and synthesis by human basophils. The inhibitory effect of flavonoids on cytokine expression by stimulated KU812 cells, a human basophilic cell line, and freshly purified peripheral blood basophils was measured by means of semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on transcriptional activation of the nuclear factor of activated T cells were assessed by means of electrophoretic mobility shift assays. Fisetin suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187-stimulated KU812 cells and basophils in response to cross-linkage of the IgE receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively) but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50) = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids examined, kaempferol and quercetin showed substantial inhibitory activities in cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812 cells. These results provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

  7. Synthesis of dansyl-labeled probe of thiophene analogue of annonaceous acetogenins for visualization of cell distribution and growth inhibitory activity toward human cancer cell lines.

    Science.gov (United States)

    Kojima, Naoto; Suga, Yuki; Matsumoto, Takuya; Tanaka, Tetsuaki; Akatsuka, Akinobu; Yamori, Takao; Dan, Shingo; Iwasaki, Hiroki; Yamashita, Masayuki

    2015-03-15

    The convergent synthesis of the dansyl-labeled probe of the thiophene-3-carboxamide analogue of annonaceous acetogenins, which shows potent antitumor activity, was accomplished by two asymmetric alkynylations of the 2,5-diformyl THF equivalent with an alkyne having a thiophene moiety and another alkyne tagged with a dansyl group. The growth inhibitory profiles toward 39 human cancer cell lines revealed that the probe retained the biological function of its mother compound, and would be useful for studying cellular activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4-oxadiazoles containing glycine and alanine hybrids with anti cancer activity.

    Science.gov (United States)

    Pidugu, Vijaya Rao; Yarla, Nagendra Sastry; Pedada, Srinivasa Rao; Kalle, Arunasree M; Satya, A Krishna

    2016-11-01

    Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biological activity. Herein, we describe the design, synthesis and biological evaluation of a series of novel 2,5-disubstituted 1,3,4-oxadiazoles (10a-10j) as class I histone deacetylase (HDAC) inhibitors. The compounds were designed and evaluated for HDAC8 selectivity using in silico docking software (Glide) and the top 10 compounds with high dock score and obeying Lipinski's rule were synthesized organically. Further the biological HDAC inhibitory and selectivity assays and anti-proliferative assays were carried out. In in silico and in vitro studies, all compounds (10a-10j) showed significant HDAC inhibition and exhibited HDAC8 selectivity. Among all tested compounds, 10b showed substantial HDAC8 inhibitory activity and better anticancer activity which is comparable to the positive control, a FDA approved drug, vorinostat (SAHA). Structural activity relation is discussed with various substitutions in the benzene ring connected on 1,3,4-oxadizole and glycine/alanine. The study warranted further investigations to develop HDAC8-selective inhibitory molecule as a drug for neoplastic diseases. Novel 1,3,4-oxadizole substituted with glycine/alanine showed HDAC8 inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity.

    Science.gov (United States)

    Mojzych, Mariusz; Tarasiuk, Paweł; Kotwica-Mojzych, Katarzyna; Rafiq, Muhammad; Seo, Sung-Yum; Nicewicz, Michał; Fornal, Emilia

    2017-12-01

    A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC 50 0.037, 0.044 and 0.042 μM, respectively, while IC 50 of thiourea is 20.9 μM.

  10. Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

    Science.gov (United States)

    Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

    2015-11-01

    A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

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

    International Nuclear Information System (INIS)

    Pons, I.

    1997-09-01

    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. Effects of Secondary Metabolites of Permafrost Bacillus sp. on Cytokine Synthesis by Human Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Kalenova, L F; Kolyvanova, S S; Bazhin, A S; Besedin, I M; Mel'nikov, V P

    2017-06-01

    We studied the effects of secondary metabolites of Bacillus sp. isolated from late Neogene permafrost on secretion of proinflammatory (TNF-α, IL-1β, IL-8, IL-2, and IFNγ) and antiinflammatory (IL-4 and IL-10) cytokines by human peripheral blood mononuclear cells. It was found that metabolites of Bacillus sp. produced more potent effect on cytokine secretion than mitogen phytohemagglutinin and metabolites of Bacillus cereus, medicinal strain IP5832. Activity of metabolites depended on the temperature of bacteria incubation. "Cold" metabolites of Bacillus sp. (isolated at -5°C) primarily induced Th1-mediated secretion of IFNγ, while "warm" metabolites (obtained at 37°C) induced Th2-mediated secretion of IL-4. The results suggest that Bacillus sp. metabolites are promising material for the development of immunomodulating drugs.

  13. The inhibitory effect of Duchesnea chrysantha extract on the development of atopic dermatitis-like lesions by regulating IgE and cytokine production in Nc/Nga mice.

    Science.gov (United States)

    Lee, Ji-Sook; Kim, In Sik; Ryu, Ji-Sun; Kim, Joo-Hwan; Kim, Jin Sook; Kim, Dong-Hee; Yun, Chi-Young

    2012-02-01

    Duchesnea chrysantha belongs to the Rosaceae family and has been used traditionally for the treatment of various diseases in Korea and other parts of East Asia. This study examined the antiinflammatory effect of Duchesnea chrysantha extract (DcE) on atopic dermatitis in vitro and in vivo. DcE inhibited the production of IL-6, IL-8 and MCP-1 in THP-1 cells and the release of IL-6 and MCP-1 in EoL-1 cells after treatment with house dust mite extract. In the in vivo experiment, Nc/Nga mice were sensitized to DNCB and then orally and dorsally administered DcE (50 mg/kg in PBS) for 3 weeks. The DcE administration significantly reduced the skin severity score when compared with the control group and inhibited the thickening of the epidermis and infiltration of inflammatory cells into the dermis. In addition, the serum IgE levels decreased markedly in the DcE-treated mice when compared with the control group. The synthesis of IL-5, IL-13, MCP-1 and eotaxin was also decreased in splenocytes of the DcE-treated group, while IFN-γ was increased in the Dc-administered group. These results may indicate that DcE attenuates the development of atopic dermatitis-like lesions by lowering the IgE and inflammatory cytokine levels, and that it is useful in drug development for the treatment of atopic dermatitis. Copyright © 2011 John Wiley & Sons, Ltd.

  14. 2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study.

    Science.gov (United States)

    Adegboye, Akande Akinsola; Khan, Khalid Mohammed; Salar, Uzma; Aboaba, Sherifat Adeyinka; Kanwal; Chigurupati, Sridevi; Fatima, Itrat; Taha, Mohammad; Wadood, Abdul; Mohammad, Jahidul Isalm; Khan, Huma; Perveen, Shahnaz

    2018-04-25

    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC 50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC 50  = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. Evidence for the involvement of a labile protein in stimulation of adrenal steroidogenesis under conditions not inhibitory to protein synthesis

    International Nuclear Information System (INIS)

    Krueger, R.J.; Orme-Johnson, N.R.

    1988-01-01

    Evidence is presented to support the hypothesis that synthesis of a labile protein is required for stimulation of steroidogenesis in rat adrenocortical cells. Amino acids L-canavanine and L-S-aminoethylcysteine, at concentrations as high as 5 mM, each inhibited steroidogenesis to a much greater extent than they inhibited protein synthesis. S-Aminoethylcysteine caused a 50% decrease in the stimulated rate of corticosterone production under conditions where incorporation of [35S]methionine into protein was unchanged. Both amino acids block stimulation of steroid synthesis at a step subsequent to the formation of cAMP and before the synthesis of progesterone. The onset of this effect, after the addition of the amino acids, on corticosterone production is quite rapid. These results provide support, that is not dependent on inhibition of protein synthesis, for the hypothesis that a labile protein mediates stimulation of steroidogenesis. Reversal of canavanine and S-aminoethylcysteine inhibition of steroidogenesis by arginine and lysine, respectively, suggests that the inhibitors are functioning as amino acid analogs. S-Aminoethylcysteine inhibits the incorporation of [3H]lysine into protein as well as inhibits steroidogenesis; further, [3H]S-aminoethylcysteine is incorporated into protein that is nonstimulatory. These results suggest that lysine residues play an essential role in the function of the labile protein or that the labile protein contains a large number of lysine residues

  16. RAGE and TGF-β1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Andreea Iren Serban

    Full Text Available AGEs accumulation in the skin affects extracellular matrix (ECM turnover and triggers diabetes associated skin conditions and accelerated skin aging. The receptor of AGEs (RAGE has an essential contribution to cellular dysfunction driven by chronic inflammatory responses while TGF-β1 is critical in both dermal homeostasis and inflammation. We investigated the contribution of RAGE and TGF-β1 to the modulation of inflammatory response and ECM turnover in AGEs milieu, using a normal fibroblast cell line. RAGE, TGF-β1, collagen I and III gene and protein expression were upregulated after exposure to AGEs-BSA, and MMP-2 was activated. AGEs-RAGE was pivotal in NF-κB dependent collagen I expression and joined with TGF-β1 to stimulate collagen III expression, probably via ERK1/2 signaling. AGEs-RAGE axis induced upregulation of TGF-β1, TNF-α and IL-8 cytokines. TNF-α and IL-8 were subjected to TGF-β1 negative regulation. RAGE's proinflammatory signaling also antagonized AGEs-TGF-β1 induced fibroblast contraction, suggesting the existence of an inhibitory cross-talk mechanism between TGF-β1 and RAGE signaling. RAGE and TGF-β1 stimulated anti-inflammatory cytokines IL-2 and IL-4 expression. GM-CSF and IL-6 expression appeared to be dependent only on TGF-β1 signaling. Our data also indicated that IFN-γ upregulated in AGEs-BSA milieu in a RAGE and TGF-β1 independent mechanism. Our findings raise the possibility that RAGE and TGF-β1 are both involved in fibrosis development in a complex cross-talk mechanism, while also acting on their own individual targets. This study contributes to the understanding of impaired wound healing associated with diabetes complications.

  17. Synthesis and Heme Polymerization Inhibitory Activity (HPIA Assay of Antiplasmodium of (1-N-(3,4-Dimethoxybenzyl-1,10-Phenanthrolinium Bromide from Vanillin

    Directory of Open Access Journals (Sweden)

    Dhina Fitriastuti

    2014-03-01

    Full Text Available The synthesis of (1-N-(3,4-dimethoxy-benzyl-1,10-phenanthrolinium bromide had been conducted from vanillin. Heme polymerization inhibitory activity assay of the synthesized antiplasmodium has also been carried out. The first step of reaction was methylation of vanillin using dimethylsulfate and NaOH. The mixture was refluxed for 2 h to yield veratraldehyde in the form of light yellow solid (79% yield. Methylation product was reduced using sodium borohydride (NaBH4 with grinding method and yielded veratryl alcohol in the form of yellow liquid (98% yield. Veratryl alcohol was brominated using PBr3 to yield yellowish black liquid (85% yield. The final step was benzylation of 1,10-phenanthroline monohydrate with the synthesized veratryl bromide under reflux condition in acetone for 14 h to afford (1-N-(3,4-dimethoxy-benzyl-1,10-phenanthrolinium bromide (84% as yellow solid with melting point of 166-177 °C. The structures of products were characterized by FT-IR, GC-MS and 1H-NMR spectrometers. The results of heme polymerization inhibitory activity assay of (1-N-(3,4-dimethoxybenzyl-1,10-phenanthrolinium bromide showed that it had IC50 HPIA of 3.63 mM, while chloroquine had IC50 of4.37 mM. These results indicated that (1-N-(3,4-dimethoxybenzyl-1,10-phenanthrolinium bromide was more potential antiplasmodium than chloroquine.

  18. Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study.

    Science.gov (United States)

    Węglarz-Tomczak, Ewelina; Burda-Grabowska, Małgorzata; Giurg, Mirosław; Mucha, Artur

    2016-11-01

    A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC 50 =1-12μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Synthesis and evaluation of the inhibitory activity of the four stereoisomers of the potent and selective human γ-glutamyl transpeptidase inhibitor GGsTop.

    Science.gov (United States)

    Watanabe, Bunta; Tabuchi, Yukiko; Wada, Kei; Hiratake, Jun

    2017-11-01

    2-Amino-4-{[3-(carboxymethyl)phenoxy](methoxy)phosphoryl}butanoic acid (GGsTop) is a potent, highly selective, nontoxic, and irreversible inhibitor of γ-glutamyl transpeptidase (GGT). GGsTop has been widely used in academic and medicinal research, and also as an active ingredient (Nahlsgen) in commercial anti-aging cosmetics. GGsTop consists of four stereoisomers due to the presence of two stereogenic centers, i.e., the α-carbon atom of the glutamate mimic (l/d) and the phosphorus atom (R P /S P ). In this study, each stereoisomer of GGsTop was synthesized stereoselectively and their inhibitory activity against human GGT was evaluated. The l- and d-configurations of each stereoisomer were determined by a combination of a chiral pool synthesis and chiral HPLC analysis. The synthesis of the four stereoisomers of GGsTop used chiral synthetic precursors that were separated by chiral HPLC on a preparative scale. With respect to the configuration of the α-carbon atom of the glutamate mimic, the l-isomer (k on =174M -1 s -1 ) was ca. 8-fold more potent than the d-isomer (k on =21.5M -1 s -1 ). In contrast, the configuration of the phosphorus atom is critical for GGT inhibitory activity. Based on a molecular modeling approach, the absolute configuration of the phosphorus atom of the active GGsTop isomers was postulated to be S P . The S P -isomers inhibited human GGT (k on =21.5-174M -1 s -1 ), while the R P -isomers were inactive even at concentrations of 0.1mM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl-N-(substituted-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Muhammad Athar Abbasi

    2018-06-01

    Full Text Available The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1. The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2 in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl-4-methylbenzensulfonamide (3.This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a–j, using N,N-dimethylformamide (DMF as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl-N-(substituted-4-methylbenzenesulfonamides (5a–j. The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl-4-methyl-N-(2-propylbenzensulfonamide (5c showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM.The docking studies of synthesized ligands 5a–j were also carried out against acetylcholinesterase (PDBID 4PQE to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors.

  1. The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.

    Science.gov (United States)

    Spencer, Juliet V

    2007-02-01

    Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.

  2. Influence of Aloe arborescens Mill. extract on selected parameters of pro-oxidant-antioxidant equilibrium and cytokine synthesis in rowers.

    Science.gov (United States)

    Basta, Piotr; Pilaczyńska-Szczęśniak, Łucja; Woitas-Ślubowska, Donata; Skarpańska-Stejnborn, Anna

    2013-08-01

    This investigation examined the effect of supplementation with Biostimine, extract from Aloe arborescens Mill. leaves, on the levels of pro-oxidant-antioxidant equilibrium markers and anti- and proinflammatory cytokines in rowers subjected to exhaustive exercise. This double-blind study included 18 members of the Polish Rowing Team. Subjects were randomly assigned to the supplemented group (n = 9), which received one ampoule of Biostimine once daily for 4 weeks, or to the placebo group (n = 9). Subjects performed a 2,000-meter-maximum test on a rowing ergometer at the beginning and end of the preparatory camp. Blood samples were obtained from the antecubital vein before each exercise test, 1 min after completing the test and after a 24-hr recovery period. Superoxide dismutase and glutathione peroxidase activity as well as the concentration of thiobarbituric acid reactive substances (TBARS) were assessed in erythrocytes. In addition, total antioxidant capacity (TAC) and creatine kinase activity were measured in plasma samples, and cytokine (IL-6, IL-10) concentrations were determined in the serum. Before and after Biostimine supplementation, exercise significantly increased the values of SOD, IL-6, IL-10, and TBARS in both groups. However, postexercise and recovery levels of TBARS were significantly lower in athletes receiving Biostimine than in controls. After supplementation, TAC was the only variable with the level being significantly higher in the supplemented group than in the placebo group. Consequently, we can conclude that Biostimine supplementation reduces the postexercise level of TBARS by increasing the antioxidant activity of plasma but has no effect on inflammatory markers.

  3. Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

    Science.gov (United States)

    Burmaoglu, Serdar; Yilmaz, Ali O; Taslimi, Parham; Algul, Oztekin; Kilic, Deryanur; Gulcin, Ilhami

    2018-02-01

    A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K i values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM against α-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against hCA II. © 2018 Deutsche Pharmazeutische Gesellschaft.

  4. Structural Modifications of Benzimidazoles via Multi-Step Synthesis and Their Impact on Sirtuin-Inhibitory Activity.

    Science.gov (United States)

    Yoon, Yeong Keng; Choon, Tan Soo

    2016-01-01

    Benzimidazole derivatives have been shown to possess sirtuin-inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole-based sirtuin inhibitors, to further investigate their structure-activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta-substituted compounds possessed markedly weaker potency than ortho- and para-substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Synthesis, structures and Helicobacter pylori urease inhibitory activity of copper(II) complexes with tridentate aroylhydrazone ligands.

    Science.gov (United States)

    Pan, Lin; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Zhu, Hailiang; Zhao, Xinlu; Qu, Dan; Niu, Fang; You, Zhonglu

    2016-06-01

    A series of new copper(II) complexes were prepared. They are [CuL(1)(NCS)] (1), [CuClL(1)]·CH3OH (2), [CuClL(2)]·CH3OH (3), [CuL(3)(NCS)]·CH3OH (4), [CuL(4)(NCS)]·0.4H2O (5), and [CuL(5)(bipy)] (6), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, 4-bromo-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide and 2-chloro-N'-(2-hydroxy-5-methoxybenzylidene)benzohydrazide, respectively, L(5) is the dianionic form of N'-(2-hydroxybenzylidene)-3-methylbenzohydrazide, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra and single crystal X-ray diffraction. The Cu atoms in complexes 1, 2, 3, 4 and 5 are coordinated by the NOO donor set of the aroylhydrazone ligands, and one Cl or thiocyanate N atom, forming square planar coordination. The Cu atom in complex 6 is in a square pyramidal coordination, with the NOO donor set of L(1), and one N atom of bipy defining the basal plane, and with the other N atom of bipy occupying the apical position. Complexes 1, 2, 3, 4 and 5 show effective urease inhibitory activities, with IC50 values of 5.14, 0.20, 4.06, 5.52 and 0.26μM, respectively. Complex 6 has very weak activity against urease, with IC50 value over 100μM. Molecular docking study of the complexes with the Helicobacter pylori urease was performed. The relationship between structures and urease inhibitory activities indicated that copper complexes with square planar coordination are better models for urease inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Benjamin L Duell

    Full Text Available Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10 in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

  7. Inhibitory noise

    Directory of Open Access Journals (Sweden)

    Alain Destexhe

    2010-03-01

    Full Text Available Cortical neurons in vivo may operate in high-conductance states, in which the major part of the neuron's input conductance is due to synaptic activity, sometimes several-fold larger than the resting conductance. We examine here the contribution of inhibition in such high-conductance states. At the level of the absolute conductance values, several studies have shown that cortical neurons in vivo are characterized by strong inhibitory conductances. However, conductances are balanced and spiking activity is mostly determined by fluctuations, but not much is known about excitatory and inhibitory contributions to these fluctuations. Models and dynamic-clamp experiments show that, during high-conductance states, spikes are mainly determined by fluctuations of inhibition, or by inhibitory noise. This stands in contrast to low-conductance states, in which excitatory conductances determine spiking activity. To determine these contributions from experimental data, maximum likelihood methods can be designed and applied to intracellular recordings in vivo. Such methods indicate that action potentials are indeed mostly correlated with inhibitory fluctuations in awake animals. These results argue for a determinant role for inhibitory fluctuations in evoking spikes, and do not support feed-forward modes of processing, for which opposite patterns are predicted.

  8. Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

    Science.gov (United States)

    Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

    2012-01-01

    The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

  9. 2-(2-(4-Benzoylpiperazin-1-ylethylisoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammadi-Farani

    2017-01-01

    Full Text Available Objective(s: Alzheimer’s disease (AD as progressive cognitive decline and the most common form of dementia is due to degeneration of the cholinergic neurons in the brain. Therefore, administration of the acetylcholinesterase (AChE inhibitors such as donepezil is the first choice for treatment of the AD. In the present study, we focused on the synthesis and anti-cholinesterase evaluation of new donepezil like analogs. Materials and Methods: A new series of phthalimide derivatives (compounds 4a-4j were synthesized via Gabriel protocol and subsequently amidation reaction was performed using various benzoic acid derivatives. Then, the corresponding anti-acetylcholinesterase activity of the prepared derivatives (4a-4j was assessed by utilization of the Ellman's test and obtained results were compared to donepezil. Besides, docking study was also carried out to explore the likely in silico binding interactions.  Results: According to the obtained results, electron withdrawing groups (Cl, F at position 3 and an electron donating group (methoxy at position 4 of the phenyl ring enhanced the acetylcholinesterase inhibitory activity. Compound 4e (m-Fluoro, IC50 = 7.1 nM and 4i (p-Methoxy, IC50 = 20.3 nM were the most active compounds in this series and exerted superior potency than donepezil (410 nM. Moreover, a similar binding mode was observed in silico for all ligands in superimposition state with donepezil into the active site of acetylcholinesterase. Conclusion: Studied compounds could be potential leads for discovery of novel anti-Alzheimer agents in the future.

  10. Macrophage migration inhibitory factor is elevated in obese adolescents

    NARCIS (Netherlands)

    Kamchybekov, Uran; Figulla, Hans R.; Gerdes, Norbert; Jung, Christian

    2012-01-01

    Objectives: The prevalence of obesity in childhood and adolescence is continuing rising. Macrophage migration inhibitory factor (MIF) participates in inflammatory and immune responses as a pro-inflammatory cytokine. The present study aimed to investigate MIF in overweight adolescents. Methods:

  11. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  12. Interactions between cytokines and nitric oxide.

    Science.gov (United States)

    Liew, F Y

    1995-01-01

    There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

  13. Macrophage migration inhibitory factor is associated with aneurysmal expansion

    DEFF Research Database (Denmark)

    Pan, Jie-Hong; Lindholt, Jes Sanddal; Sukhova, Galina K

    2003-01-01

    Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution o...... of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions.......Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution...

  14. Synthesis of Amide and Ester Derivatives of Cinnamic Acid and Its Analogs: Evaluation of Their Free Radical Scavenging and Monoamine Oxidase and Cholinesterase Inhibitory Activities.

    Science.gov (United States)

    Takao, Koichi; Toda, Kazuhiro; Saito, Takayuki; Sugita, Yoshiaki

    2017-01-01

    A series of cinnamic acid derivatives, amides (1-12) and esters (13-22), were synthesized, and structure-activity relationships for antioxidant activity, and monoamine oxidases (MAO) A and B, acetylcholinesterase, and butyrylcholinesterase (BChE) inhibitory activities were analyzed. Among the synthesized compounds, compounds 1-10, 12-18, and rosmarinic acid (23), which contained catechol, o-methoxyphenol or 5-hydroxyindole moieties, showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Compounds 9-11, 15, 17-22 showed potent and selective MAO-B inhibitory activity. Compound 20 was the most potent inhibitor of MAO-B. Compounds 18 and 21 showed moderate BChE inhibitory activity. In addition, compound 18 showed potent antioxidant activity and MAO-B inhibitory activity. In a comparison of the cinnamic acid amides and esters, the amides exhibited more potent DPPH free radical scavenging activity, while the esters showed stronger inhibitory activities against MAO-B and BChE. These results suggested that cinnamic acid derivatives such as compound 18, p-coumaric acid 3,4-dihydroxyphenethyl ester, and compound 20, p-coumaric acid phenethyl ester, may serve as lead compounds for the development of novel MAO-B inhibitors and candidate lead compounds for the prevention or treatment of Alzheimer's disease.

  15. Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

    Directory of Open Access Journals (Sweden)

    Ghodsi Mohammadi Ziarani

    2013-01-01

    Full Text Available A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.ResultsReactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 muM.DiscussionThe compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

  16. Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

    Directory of Open Access Journals (Sweden)

    Ziarani Ghodsi Mohammadi

    2013-01-01

    Full Text Available Abstract Background A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported. Results Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM. Discussion The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

  17. Synthesis and 5α-Reductase Inhibitory Activity of C21 Steroids Having 1,4-diene or 4,6-diene 20-ones and 4-Azasteroid 20-Oximes

    Directory of Open Access Journals (Sweden)

    Eunsook Ma

    2011-12-01

    Full Text Available The synthesis and evaluation of 5α-reductase inhibitory activity of some 4-azasteroid-20-ones and 20-oximes and 3β-hydroxy-, 3β-acetoxy-, or epoxy-substituted C21 steroidal 20-ones and 20-oximes having double bonds in the A and/or B ring are described. Inhibitory activity of synthesized compounds was assessed using 5α-reductase enzyme and [1,2,6,7-3H]testosterone as substrate. All synthesized compounds were less active than finasteride (IC50: 1.2 nM. Three 4-azasteroid-2-oximes (compounds 4, 6 and 8 showed good inhibitory activity (IC50: 26, 10 and 11 nM and were more active than corresponding 4-azasteroid 20-ones (compounds 3, 5 and 7. 3β-Hydroxy-, 3β-acetoxy- and 1α,2α-, 5α,6α- or 6α,7α-epoxysteroid-20-one and -20-oxime derivatives having double bonds in the A and/or B ring showed no inhibition of 5α-reductase enzyme.

  18. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  19. Synthesis and enzyme inhibitory studies of some new N-alkylated/aralkylated N-(4-ethoxyphenyl)-2,3-drobenzo-(1,4)-dioxin-6-sulfonamides

    International Nuclear Information System (INIS)

    Abbasi, M.A.; Islam, M.; Rehman, A.U.; Siddiqui, S.Z.

    2016-01-01

    The research endeavor was aimed to synthesize N-alkyl/aralkylated-N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6 sulfonamides and to evaluate their enzyme inhibitory potential. The target molecules were synthesized in two steps. The first step involved the reaction of 4-ethoxyaniline (1) with N-2,3-dihydrobenzo(1,4)-dioxin-6-sulfonyl chloride (2) under dynamic pH control maintained by 10% aqueous Na/sub 2/CO/sub 3/ to yield N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6-sulfonamide (3). In second step parent compound 3 was reacted with various alkyl/aralkyl halides (4a-l) in N,N'-dimethylformamide and catalytic amount of lithium hydride to accomplish some new N-alkyl/aralkylated-N-(4-ethoxyphenyl)-2,3-dihydrobenzo-(1,4)-dioxine-6 sulfonamides (5a-l). Probable structures of the synthesized compounds were characterized by contemporary spectral techniques i.e. IR, 1H-NMR and EIMS and were finally evaluated for enzyme inhibitory potential against a-glucosidase and urease. The synthesized compounds exhibited moderate to weak therapeutic potential throughout the series. (author)

  20. Inhibitory Role of Greatwall-Like Protein Kinase Rim15p in Alcoholic Fermentation via Upregulating the UDP-Glucose Synthesis Pathway in Saccharomyces cerevisiae.

    Science.gov (United States)

    Watanabe, Daisuke; Zhou, Yan; Hirata, Aiko; Sugimoto, Yukiko; Takagi, Kenichi; Akao, Takeshi; Ohya, Yoshikazu; Takagi, Hiroshi; Shimoi, Hitoshi

    2016-01-01

    The high fermentation rate of Saccharomyces cerevisiae sake yeast strains is attributable to a loss-of-function mutation in the RIM15 gene, which encodes a Greatwall-family protein kinase that is conserved among eukaryotes. In the present study, we performed intracellular metabolic profiling analysis and revealed that deletion of the RIM15 gene in a laboratory strain impaired glucose-anabolic pathways through the synthesis of UDP-glucose (UDPG). Although Rim15p is required for the synthesis of trehalose and glycogen from UDPG upon entry of cells into the quiescent state, we found that Rim15p is also essential for the accumulation of cell wall β-glucans, which are also anabolic products of UDPG. Furthermore, the impairment of UDPG or 1,3-β-glucan synthesis contributed to an increase in the fermentation rate. Transcriptional induction of PGM2 (phosphoglucomutase) and UGP1 (UDPG pyrophosphorylase) was impaired in Rim15p-deficient cells in the early stage of fermentation. These findings demonstrate that the decreased anabolism of glucose into UDPG and 1,3-β-glucan triggered by a defect in the Rim15p-mediated upregulation of PGM2 and UGP1 redirects the glucose flux into glycolysis. Consistent with this, sake yeast strains with defective Rim15p exhibited impaired expression of PGM2 and UGP1 and decreased levels of β-glucans, trehalose, and glycogen during sake fermentation. We also identified a sake yeast-specific mutation in the glycogen synthesis-associated glycogenin gene GLG2, supporting the conclusion that the glucose-anabolic pathway is impaired in sake yeast. These findings demonstrate that downregulation of the UDPG synthesis pathway is a key mechanism accelerating alcoholic fermentation in industrially utilized S. cerevisiae sake strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Beneficial effects of cytokine induced hyperlipidemia.

    Science.gov (United States)

    Feingold, K R; Hardardóttir, I; Grunfeld, C

    1998-01-01

    Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and

  2. Synthesis of tumor necrosis factor α for use as a mirror-image phage display target.

    Science.gov (United States)

    Petersen, Mark E; Jacobsen, Michael T; Kay, Michael S

    2016-06-21

    Tumor Necrosis Factor alpha (TNFα) is an inflammatory cytokine that plays a central role in the pathogenesis of chronic inflammatory disease. Here we describe the chemical synthesis of l-TNFα along with the mirror-image d-protein for use as a phage display target. The synthetic strategy utilized native chemical ligation and desulfurization to unite three peptide segments, followed by oxidative folding to assemble the 52 kDa homotrimeric protein. This synthesis represents the foundational step for discovering an inhibitory d-peptide with the potential to improve current anti-TNFα therapeutic strategies.

  3. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  4. Development of chronic colitis is dependent on the cytokine MIF

    NARCIS (Netherlands)

    de Jong, Y. P.; Abadia-Molina, A. C.; Satoskar, A. R.; Clarke, K.; Rietdijk, S. T.; Faubion, W. A.; Mizoguchi, E.; Metz, C. N.; Alsahli, M.; ten Hove, T.; Keates, A. C.; Lubetsky, J. B.; Farrell, R. J.; Michetti, P.; van Deventer, S. J.; Lolis, E.; David, J. R.; Bhan, A. K.; Terhorst, C.; Sahli, M. A.

    2001-01-01

    The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis.

  5. Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

    Science.gov (United States)

    2013-01-01

    Background Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. Results Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. Conclusions Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. PMID:23758724

  6. Synthesis, Docking and Acetylcholinesterase Inhibitory Assessment of 2-(2-(4-Benzylpiperazin-1-YlEthylIsoindoline-1,3-Dione Derivatives with Potential Anti-Alzheimer Effects

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammadi-Farani

    2013-06-01

    Full Text Available Background:Alzheimer’s disease (AD as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease.Results:Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-ylethylisoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM compared to donepezil (IC50 = 0.14 ± 0.03 μM. The results of the enzyme inhibition test (Ellman test showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta afforded a favorable potency (IC50 = 5.5 ± 0.7 μM. Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a.Conclusions:Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents.

  7. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  8. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

  9. Amniotic fluid inflammatory cytokines

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob

    2013-01-01

    The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy.......The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy....

  10. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  11. Recombinant Cytokines from Plants

    Czech Academy of Sciences Publication Activity Database

    Sirko, A.; Vaněk, Tomáš; Gora-Sochacka, A.; Redkiewicz, P.

    2011-01-01

    Roč. 12, č. 6 (2011), s. 3536-3552 ISSN 1661-6596 Institutional research plan: CEZ:AV0Z50380511 Keywords : cytokines * pharmaceutical proteins * plant-based production systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.598, year: 2011

  12. Cytokine loops driving senescence

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk; Lukáš, Jan

    2008-01-01

    Roč. 10, č. 8 (2008), s. 887-889 ISSN 1465-7392 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * cytokines * autocrine feedback loop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 17.774, year: 2008

  13. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  14. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

  15. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    Peremot S. D

    2016-12-01

    , IL-10, INF-γ, TNF-α in blood serum was conducted by the method of solid-phase enzyme-linked immunosorbent assay, population structure of lymphocytes with different antigenic determinants (CD3+, CD4+, CD8+, CD16/56, CD19+, СD95+ was determined by monoclonal antibodies by cytofluorimetric assay. Obtained data processing was conducted with the use of parametric and non-parametric methods of biostatistics by programs EXEL-2003® and Biostatistics 4.03. Results and discussion. The data obtained indicates the disbalance in their system, which above all is characterized by a considerable level increase of pro-inflammatory IL-6 up to 134,09 ± 22,72 pg/ml (control level 11,83 ± 1,64 pg/ml and in relation to moderate growth of levels of IL-2 та TNF-α at subacute myocarditis. Such increase in level of IL-6 can take place due to the change of pro-inflammatory effect to anti-inflammatory in a remote period. In a complex with IL-10 IL-6 limits the secretion of TNF-α. For this reason, its level remains high at chronic herpesvirus myocarditis and exceeds the level of the control group by over 8 times. In addition, there is an increase of levels of anti-inflammatory IL-4, IL-10 cytokines at the chronic form of herpesvirus myocarditis course by 2,9 and 3,1 times respectively. At the same time, the level of IL-10 increased not only in comparison with the level of the control group but also almost 2 times exceeded the proper index at subacute myocarditis. Instead of the predicted INF-γ level rise, its decline was discovered, in patients with subacute course the index value was the lowest. This phenomenon can be the result of mast cells activity and in its turn influences the synthesis of collogen and processes of myocardium remodeling. Analysis of sub-population composition of lymphocytes discovered the increase in number of CD3+CD95+ lymphocytes of peripheral blood at myocarditis, especially in the group of patients with subacute herpesvirus myocarditis with its level

  16. Inflammation and cancer: macrophage migration inhibitory factor (MIF)--the potential missing link.

    LENUS (Irish Health Repository)

    Conroy, H

    2010-11-01

    Macrophage migration inhibitory factor (MIF) was the original cytokine, described almost 50 years ago and has since been revealed to be an important player in pro-inflammatory diseases. Recent work using MIF mouse models has revealed new roles for MIF. In this review, we present an increasing body of evidence implicating the key pro-inflammatory cytokine MIF in specific biological activities related directly to cancer growth or contributing towards a microenvironment favouring cancer progression.

  17. [Polymorphism of TNF-alpha (308 A/G), IL-10 (1082 A/G, 819 C/T 592 A/C), IL-6 (174 G/C), and IFN-gamma (874 A/T); genetically conditioned cytokine synthesis level in children with diabetes type 1].

    Science.gov (United States)

    Siekiera, Urszula; Jarosz-Chobot, P; Janusz, J; Koehler, Brygida

    2002-01-01

    Type 1 diabetes is a genetically conditioned autoimmune disease. Genes that account for strong clustering of the disease susceptibility are located within the HLA region. There is also considerable individual variation in the immune response and role of cytokine genes in the disease predisposition. The aim of our research was identification of the genetically controlled TNF-alpha, IL-10, IL-6, IFN-gamma secretion profile in children with diabetes type 1. We have examined 36 children with diabetes type 1 and 36 healthy individuals. DNA was extracted from mononuclear peripheral blood cells. For identification of the cytokine polymorphism PCR-SSP method was used. Patients with diabetes type 1 differ from the group of healthy persons in the cytokine synthesis level and in the cytokine genotypes distribution. Genotype TNF-alpha (A/G) as well as IL-10 (ATA/ATA) was found only in group of children with diabetes but not in the control group. Genotypes IL-10 (GCC/GCC), IL-6 (C/C), IFN-gamma (T/T) were observed with decreased frequency in children with diabetes type 1. No differences between patients and control group in the frequency of IL-10 (GCC/ACC) (GCC/ATA), (ACC/ACC) (ACC/ATA) IL-6 (G/G), (G/C) and IFN-gamma (T/A), (A/A) genotypes were observed. Children with diabetes type 1 were more frequent "high producers" of TNF-alpha and IL-6. It is possible to us molecular method to estimate the genetically controlled immune reactivity. It is a very important immunogenetic factor of the disease predisposition.

  18. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J

    2013-01-01

    ) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... stacking method that uses clustered variance-covariance estimation allowing homogeneous (Stackc) or inhomogeneous (Stackh) variances. We compare it with direct estimation of the bivariate Tobit likelihood function (Bitobit) and multiple imputation. We assess sensitivity to inhomogeneity and non...

  19. Inhibitory effects of Trypanosoma cruzi sialoglycoproteins on CD4+ T cells are associated with increased susceptibility to infection.

    Directory of Open Access Journals (Sweden)

    Marise Pinheiro Nunes

    Full Text Available BACKGROUND: The Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens characterized by decreased IL-2 synthesis. Trypanosoma cruzi mucin (Tc Muc has been implicated in this phenomenom. These molecules contain a unique type of glycosylation consisting of several sialylated O-glycans linked to the protein backbone via N-acetylglucosamine residues. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluated the ability of Tc Muc to modulate the activation of CD4(+ T cells. Our data show that cross-linking of CD3 on naïve CD4(+ T cells in the presence of Tc Muc resulted in the inhibition of both cytokine secretion and proliferation. We further show that the sialylated O-Linked Glycan residues from tc mucin potentiate the suppression of T cell response by inducing G1-phase cell cycle arrest associated with upregulation of mitogen inhibitor p27(kip1. These inhibitory effects cannot be reversed by the addition of exogenous IL-2, rendering CD4(+ T cells anergic when activated by TCR triggering. Additionally, in vivo administration of Tc Muc during T. cruzi infection enhanced parasitemia and aggravated heart damage. Analysis of recall responses during infection showed lower frequencies of IFN-γ producing CD4(+ T cells in the spleen of Tc Muc treated mice, compared to untreated controls. CONCLUSIONS/SIGNIFICANCE: Our results indicate that Tc Muc mediates inhibitory efects on CD4(+ T expansion and cytokine production, by blocking cell cycle progression in the G1 phase. We propose that the sialyl motif of Tc Muc is able to interact with sialic acid-binding Ig-like lectins (Siglecs on CD4(+ T cells, which may allow the parasite to modulate the immune system.

  20. Structural studies on leukaemia inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Norton, R.S.; Maurer, T.; Smith, D.K. [Biomolecular Research Institute, Parville (Australia); Nicola, N.A. [Institute of Medical Research, Melbourne (Australia)

    1994-12-01

    Leukaemia Inhibitory Factor (LIF) is a pleiotropic cytokine that acts on a wide range of target cells, including mega-karyocytes, osteoblasts, hepatocytes, adipocytes, neurons, embryonic stem cells, and primordial germ cells. Many of its activities are shared with other cytokines, particularly interleukin-6, oncostatin-M, ciliary neurotrophic factor, and granulocyte colony-stimulating factor (G-CSF). Although secreted in vivo as a glycoprotein, nonglycosylated recombinant protein expressed in E. coli is fully active and has been used in our nuclear magnetic resonance (NMR) studies of the three-dimensional structure and structure-function relationships of LIF. With 180 amino acids and a molecular mass of about 20 kDa, OF is too large for direct structure determination by two-dimensional and three-dimensional {sup 1}HNMR. It is necessary to label the protein with the stable isotopes {sup 15}N and {sup 13}C and employ heteronuclear three-dimensional NMR in order to resolve and interpret the spectral information required for three-dimensional structure determination. This work has been undertaken with both human LIF and a mouse-human chimaera that binds to the human LIF receptor with the same affinity as the human protein and yet expresses in E. coli at much higher levels. Sequence-specific resonance assignments and secondary structure elements for these proteins will be presented and progress towards determination of their three-dimensional structures described.

  1. Class I Cytokine Receptors

    DEFF Research Database (Denmark)

    Steinocher, Helena

    , the minimal determinants for specificity between membrane spanning helices were investigated with small artificial low complexity peptides, prior found to activate the EPOR in cells. The placement of single methyl group in the so called transmembrane aptamers (traptamers) determined the stabilizing effect...... characteristics of membrane spanning helices, was designed and hGHR TMD and hEPOR TMD produced in sufficient amounts for spectroscopic investigations. The isolated hGHR TMD was revealed to associate in dimeric complexes in detergent micelles and first presumptions about the dimer interface could be made. Further...... the traptamers on the hEPOR TMD dimeric complex in detergent micelles. To gain a better understanding of hGHR regulation a point mutation in the hGHR intracellular domain (ICD), which has recently been linked to lung cancer, was characterized. The mutation was found to decrease binding of suppressor of cytokine...

  2. FEATURES OF CYTOKINE PRODUCTION IN PATIENTS WITH RECURRENT HERPETIC INFECTION

    Directory of Open Access Journals (Sweden)

    I. A. Novikovа

    2013-01-01

    Full Text Available Abstract. Cytokines play an important role in resistance to herpesvirus infections. Therefore, studies of cytokine profile are necessary in recurrent herpetic infection. However, functional studies of cytokine network upon remission of the disease yielded controversial results. In this paper, we provide some results concerning comprehensive evaluation of ex vivo cytokine production by whole blood leukocytes drawn from 15 patients observed during clinical remission of recurrent Herpes Simplex virus infection. We have found a decrease of IL-1β, IL-8 and IL-10 production, as well as imbalance of cytokine profile, with predominance of IFNγ and IL-8 synthesis over IL-10 production, along with increased IL-4 and IL-13 levels to IL-1β contents. Differently directed correlations between the content of activated lymphocytes (CD3+HLA-DR+ and CD3+CD4+CD25+, natural killers (СD3-СD16/56+, NKT-cells and cytokine production levels were found in the groups of patients and healthy individuals. These differences may be due to shifts in major cytokineproducing populations in herpesvirus infections.

  3. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficul...

  4. Cytokines and uveitis, a review

    NARCIS (Netherlands)

    de Vos, A. F.; Hoekzema, R.; Kijlstra, A.

    1992-01-01

    Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8

  5. Serum Macrophage Migration Inhibitory Factor in the Prediction of Preterm Delivery

    DEFF Research Database (Denmark)

    Pearce, Brad; Garvin, Sicily; Grove, Jakob

    2008-01-01

    Objective: Macrophage migration inhibitory factor (MIF) is a soluble mediator that helps govern the interaction between cytokines and stress hormones (e.g. cortisol). We determined if maternal MIF levels predicted subsequent preterm delivery (PTD). Study Design: A nested case-control study...

  6. Human keratinocyte sensitivity towards inflammatory cytokines varies with culture time

    Directory of Open Access Journals (Sweden)

    G. Elliott

    1992-01-01

    Full Text Available Proliferating keratinocyte cultures have been reported to synthesize higher concentrations of prostaglandin (PG E than confluent ones. As interleukin-1 (IL-1 stimulates keratinocyte PGE synthesis we investigated whether the degree of confluency of the keratinocyte culture modified the response of the cells to IL-1. It was found that IL-1α (100 U/ml stimulated PGE2 synthesis by proliferating (7 days in culture but not differentiating (14 days in culture keratinocytes. Similar effects were observed using tumour necrosis factor-α. Both arachidonic acid (AA and the calcium ionophore A23187 stimulated PGE2 synthesis by 7 and 14 day cultures although the increase was greatest when 7 day cultures were used. Our data indicate that there is a specific down-regulation of the mechanism(s by which some inflammatory cytokines stimulate keratinocyte eicosanoid synthesis as cultured keratinocytes begin to differentiate.

  7. 5-Thio-D-glycopyranosylamines and their amidinium salts as potential transition-state mimics of glycosyl hydrolases: synthesis, enzyme inhibitory activities, X-ray crystallography, and molecular modeling

    DEFF Research Database (Denmark)

    Kavlekar, Lizie M.; Kuntz, Douglas A.; Wen, Xin

    2005-01-01

    The synthesis of new glycosidase inhibitors, namely, the glycosylamines of 5-thioglucose and 5-thiomannose and their corresponding amidinium salts are described. We report also the crystal structures of 5-thio-D-mannopyranosyl amine 1 and 5-thio-D-mannopyranosylamidinium bromide 2 bound in the en...

  8. Synthesis, crystal structures, molecular docking, in vitro monoamine oxidase-B inhibitory activity of transition metal complexes with 2-{4-[bis (4-fluorophenyl)methyl]piperazin-1-yl} acetic acid

    Science.gov (United States)

    Yang, Dan-dan; Wang, Riu; Zhu, Jin-long; Cao, Qi-yue; Qin, Jie; Zhu, Hai-liang; Qian, Shao-song

    2017-01-01

    Three novel complexes, [Cu(L)2(H2O)](1), [Zn(L)2(H2O)2]·CH3OH·1.5H2O(2), and [Ni(L)2(H2O)1.8]·CH3OH·1.2H2O (3) (HL = 2-{4-[bis(4-fluorophenyl)methyl]pipera-zin-1-yl} acetic acid), were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential Monoamine oxidase B inhibitory activity. All acquired compounds were tested against rat brain MAO-B in vitro. In accordance with the result of calculation, it showed complex 1 (IC50 = 1.85 ± 0.31 μM) have good inhibitory activity against MAO-B at the same micromolar concentrations with positive control Iproniazid Phosphate (IP, IC50 = 7.59 ± 1.17 μM). These results indicated that complex 1 was a potent MAO-B inhibitor.

  9. Lemongrass and citral effect on cytokines production by murine macrophages.

    Science.gov (United States)

    Bachiega, Tatiana Fernanda; Sforcin, José Maurício

    2011-09-01

    Cymbopogon citratus (DC) Stapf (Poaceae-Gramineae), an herb commonly known as lemongrass (LG), is an important source of ethnomedicines as well as citral, the major constituent of Cymbopogon citratus, used in perfumery, cosmetic and pharmaceutical industries for controlling pathogens. Thus, the goal of this work was to analyze the effect of LG and citral on cytokines production (IL-1β, IL-6 and IL-10) in vitro, as well as before or after LPS incubation. Peritoneal macrophages from BALB/c mice were treated with LG or citral in different concentrations for 24h. The concentrations that inhibited cytokines production were tested before or after macrophages challenge with LPS, in order to evaluate a possible anti-inflammatory action. Supernatants of cell cultures were used for cytokines determination by ELISA. As to IL-1β, only citral inhibited its release, exerting an efficient action before LPS challenge. LG and citral inhibited IL-6 release. Cymbopogon citratus showed inhibitory effects only after LPS challenge, whereas citral prevented efficiently LPS effects before and after LPS addition. Citral inhibited IL-10 production and although LG did not inhibit its production, the concentration of 100 μg/well was tested in the LPS-challenge protocol, because it inhibited IL-6 production. LG inhibited LPS action after macrophages incubation with LPS, while citral counteracted LPS action when added before or after LPS incubation. LG exerted an anti-inflammatory action and citral may be involved in its inhibitory effects on cytokines production. We suggest that a possible mechanism involved in such results could be the inhibition of the transcription factor NF-κB. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

    Science.gov (United States)

    Papaxanthos-Roche, A; Taupin, J L; Mayer, G; Daniel, J Y; Moreau, J F

    1994-09-01

    In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

  11. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes......-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle...

  12. Design, Synthesis and Cytotoxic Evaluation of Novel Chalcone Derivatives Bearing Triazolo[4,3-a]-quinoxaline Moieties as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

    Directory of Open Access Journals (Sweden)

    Mohamed Alswah

    2017-12-01

    Full Text Available A series of hybrid of triazoloquinoxaline-chalcone derivatives 7a–k were designed, synthesized, fully characterized, and evaluated for their cytotoxic activity against three target cell lines: human breast adenocarcinoma (MCF-7, human colon carcinoma (HCT-116, and human hepatocellular carcinoma (HEPG-2. The preliminary results showed that some of these chalcones like 7b–c, and 7e–g exhibited significant antiproliferative effects against most of the cell lines, with selective or non-selective behavior, indicated by IC50 values in the 1.65 to 34.28 µM range. In order to investigate the mechanistic aspects of these active compounds, EGFR TK and tubulin inhibitory activities were measured as further biological assays. The EGFR TK assay results revealed that the derivatives 7a–c, 7e, and 7g could inhibit the EGFR TK in the submicromolar range (0.093 to 0.661 µM. Moreover, an antitubulin polymerization effect was noted for the active derivatives compared to the reference drug colchicine, with compounds 7e and 7g displaying 14.7 and 8.4 micromolar activity, respectively. Furthermore, a molecular docking study was carried out to explain the observed effects and the binding modes of these chalcones with the EGFR TK and tubulin targets.

  13. Biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives, in vitro α-amylase inhibitory activity and in silico studies.

    Science.gov (United States)

    Taha, Muhammad; Imran, Syahrul; Ismail, Nor Hadiani; Selvaraj, Manikandan; Rahim, Fazal; Chigurupati, Sridevi; Ullah, Hayat; Khan, Fahad; Salar, Uzma; Javid, Muhammad Tariq; Vijayabalan, Shantini; Zaman, Khalid; Khan, Khalid Mohammed

    2017-10-01

    A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1 H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC 50 =0.38±0.82µM) and 23 (IC 50 =1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC 50 =1.77-2.98µM when compared with the standard acarbose (IC 50 =1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: As potential leads for the management of type-II diabetes mellitus.

    Science.gov (United States)

    Taha, Muhammad; Rahim, Fazal; Imran, Syahrul; Ismail, Nor Hadiani; Ullah, Hayat; Selvaraj, Manikandan; Javid, Muhammad Tariq; Salar, Uzma; Ali, Muhammad; Khan, Khalid Mohammed

    2017-10-01

    Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as 1 H NMR, EI-MS, and 13 C NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC 50 =2.00±0.01-292.40±3.16μM as compared to standard acarbose (IC 50 =895.09±2.04µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

    Science.gov (United States)

    Estes, D M; Tuo, W; Brown, W C; Goin, J

    1998-12-01

    In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

  16. INHIBITORY EFFECT OF SALVIA SCLAREA

    African Journals Online (AJOL)

    rakoe

    2011-11-02

    Nov 2, 2011 ... This study demonstrated anti-herpes simplex virus (HSV) activity of lavender, sage and ... Green monkey kidney cells were protected from HSV-2 infection by ... The highest inhibitory effect against HSV-2 was observed after treatment ..... some nuclear-replicating eukaryotic DNA viruses with large genomes.

  17. Inhibitory control in childhood stuttering

    NARCIS (Netherlands)

    Eggers, K.; de Nil, L.; Van den Bergh, B.R.H.

    2013-01-01

    Purpose The purpose of this study was to investigate whether previously reported parental questionnaire-based differences in inhibitory control (IC; Eggers, De Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using a computer task. Method Participants were 30 children who

  18. Cytokine Correlations in Youth with Tic Disorders

    OpenAIRE

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K.

    2015-01-01

    Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder.

  19. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.; Garssen, J.; Verster, J.C.

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the

  20. Synthesis, characterization and inhibitory activities of (4-N3[3,5-3H]Phe10)PKI(6-22)amide and its precursors: photoaffinity labeling peptides for the active site of cyclic AMP-dependent protein kinase.

    Science.gov (United States)

    Katz, B M; Lundquist, L J; Walsh, D A; Glass, D B

    1989-06-01

    PKI(6-22)amide is a 17 residue peptide corresponding to the active portion of the heat-stable inhibitor of cAMP-dependent protein kinase. The peptide is a potent (Ki = 1.6 nM), competitive inhibitor of the enzyme. The photoreactive peptide analog (4-azidophenylalanine10)PKI(6-22)amide was synthesized in both its non-radiolabeled and tritiated forms by chemical modification of precursor peptides that were prepared by stepwise solid-phase synthesis. (4-Amino[3,5-3H]phenylalanine10)PKI(6-22)amide, the precursor for the radiolabeled arylazide peptide, was obtained by catalytic reduction of the corresponding peptide containing the 3,5-diiodo-4-aminophenylalanine residue at position 10. The purified PKI peptides were analyzed by HPLC, amino acid analysis, and u.v. spectra. In the dark, (4-azidophenylalanine10)PKI(6-22)amide inhibited the catalytic subunit of cAMP-dependent protein kinase with a Ki value of 2.8 nM. The photoreactivity of the arylazide peptide was demonstrated by time-dependent u.v. spectral changes on exposure to light. Photolysis of the catalytic subunit (4-azido[3,5-3H]phenylalanine10)PKI(6-22)amide complex resulted in specific covalent labeling of the enzyme. The data indicate that this peptide is a useful photoaffinity labeling reagent for the active site of the protein kinase.

  1. Cytokine Response to Exercise and Its Modulation

    OpenAIRE

    Katsuhiko Suzuki

    2018-01-01

    Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia) and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidat...

  2. ELEVATED CIRCULATING LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN POLYCYSTIC OVARY SYNDROME

    OpenAIRE

    González, Frank; Rote, Neal S.; Minium, Judi; Weaver, Amy L.; Kirwan, John P.

    2010-01-01

    Women with Polycystic Ovary Syndrome (PCOS) have chronic low level inflammation which can increase the risk of atherogenesis. We evaluated the status of circulating macrophage migration inhibitory factor (MIF), a proinflammatory cytokine involved in atherogenesis, in women with PCOS and weight-matched controls. Two-way analysis of variance models adjusted for age were fit to evaluate the effect of PCOS status (PCOS vs. controls) and weight-class (obese vs. lean) on MIF and other parameters. M...

  3. Improved survival of mesenchymal stem cells by macrophage migration inhibitory factor

    OpenAIRE

    Xia, Wenzheng; Xie, Congying; Jiang, Miaomiao; Hou, Meng

    2015-01-01

    Macrophage migration inhibitory factor (MIF) is a critical inflammatory cytokine that was recently associated with progenitor cell survival and potently inhibits apoptosis. We examined the protective effect of MIF on hypoxia/serum deprivation (SD)-induced apoptosis of mesenchymal stem cells (MSCs), as well as the possible mechanisms. MSCs were obtained from rat bone marrow and cultured in vitro. Apoptosis was induced by culturing MSCs under hypoxia/SD conditions for up to 24?h and assessed by...

  4. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  5. Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling.

    Science.gov (United States)

    Feener, Edward P; Rosario, Felicia; Dunn, Sarah L; Stancheva, Zlatina; Myers, Martin G

    2004-06-01

    Jak family tyrosine kinases mediate signaling by cytokine receptors to regulate diverse biological processes. Although Jak2 and other Jak kinase family members are phosphorylated on numerous sites during cytokine signaling, the identity and function of most of these sites remains unknown. Using tandem mass spectroscopic analysis of activated Jak2 protein from intact cells, we identified Tyr(221) and Tyr(570) as novel sites of Jak2 phosphorylation. Phosphorylation of both sites was stimulated by cytokine treatment of cultured cells, and this stimulation required Jak2 kinase activity. While we observed no gross alteration of signaling upon mutation of Tyr(221), Tyr(570) lies within the inhibitory JH2 domain of Jak2, and mutation of this site (Jak2(Y570F)) results in constitutive Jak2-dependent signaling in the absence of cytokine stimulation and enhances and prolongs Jak2 activation during cytokine stimulation. Mutation of Tyr(570) does not alter the ability of SOCS3 to bind or inhibit Jak2, however. Thus, the phosphorylation of Tyr(570) in vivo inhibits Jak2-dependent signaling independently of SOCS3-mediated inhibition. This Tyr(570)-dependent mechanism of Jak2 inhibition likely represents an important mechanism by which cytokine function is regulated.

  6. In vitro and in vivo assessment of inhibitory effect of stevioside on pro-inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Jatuporn Noosud

    2017-02-01

    Full Text Available Objective: Stevioside is a natural non-caloric sweetener which has been reported to have anti-inflammatory activity.  The aim of  the present study was to examine in vitro and in vivo effects of  stevioside on rats  plasma levels of tumor necrosis factor- α (TNF-α,  interleukin-1β (IL-1β, TNF-α and IL-1β release from lipopolysaccharide(LPS-stimulated rat peripheral blood mononuclear cells (PBMCs. Materials and Methods: Male wistar rats weighing between 170-220 g were given stevioside (0, 500 and 1000 mg/kg BW/day for 6 weeks. Mononuclear cells were separated from peripheral blood samples.  TNF-α and IL-1β levels in plasma and the release of TNF-α and IL-1β from PBMCs were determined using rat enzyme-linked immunosorbent assay (ELISA kits. Results:  Plasma levels of TNF-α and IL-1β were found to be non-detectable in control and groups treated with 500 and 1000 mg/kg of stevioside.  Regarding TNF-α release from LPS-stimulated    PBMCs, rats that were orally fed with 500 and 1000 mg/kg of stevioside were significantly different (p

  7. The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

    due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also...

  8. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  9. Studies on the biosynthesis of macrophage migration inhibitory factor in delayed hypersensitivity, 1

    International Nuclear Information System (INIS)

    Mizoguchi, Yasuhiro; Yamamoto, Sukeo; Morisawa, Seiji

    1973-01-01

    Specific antigenic stimulation of sensitized lymphocytes leads to the production of macrophage migration inhibitory factor (MIF). Production of MIF is inhibited by mitomycin C, actinomycin D, and puromycin. These inhibition effects are studied by using thymidine- 3 H. The first two of these antibiotics only inhibit MIF production when added to the culture medium at a very early stage of antigenic stimulation. In contrast, puromycin exerts its inhibitory effect several hours after the antigenic stimulation, but not at an earlier stage. MIF behaves like a protein, so it seems likely that synthesis of RNA is necessary for MIF formation and MIF synthesis may start as early as a few hours after specific antigenic activation of the sensitized lymphocytes. The inhibitory effects of the antibiotics are discussed in relation to the kinetics of MIF production. (author)

  10. Development of chronic colitis is dependent on the cytokine MIF.

    Science.gov (United States)

    de Jong, Y P; Abadia-Molina, A C; Satoskar, A R; Clarke, K; Rietdijk, S T; Faubion, W A; Mizoguchi, E; Metz, C N; Alsahli, M; ten Hove, T; Keates, A C; Lubetsky, J B; Farrell, R J; Michetti, P; van Deventer, S J; Lolis, E; David, J R; Bhan, A K; Terhorst, C; Sahli, M A

    2001-11-01

    The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

  11. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

    2011-01-01

    GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were...

  12. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while...... hypoglycaemia may be due to direct effects of similar molecules on glucose metabolism. These molecules appear to be phospholipids and we suggest that when fully characterized they might form the basis of antitoxic therapy for malaria....

  13. Cytokines and cytokine networks target neurons to modulate long-term potentiation.

    Science.gov (United States)

    Prieto, G Aleph; Cotman, Carl W

    2017-04-01

    Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Directory of Open Access Journals (Sweden)

    Nádia Rezende Barbosa Raposo

    2012-10-01

    Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

  15. Interleukin-4 but not interleukin-10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes.

    Science.gov (United States)

    Dechanet, J; Taupin, J L; Chomarat, P; Rissoan, M C; Moreau, J F; Banchereau, J; Miossec, P

    1994-12-01

    The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.

  16. Degree of synchronization modulated by inhibitory neurons in clustered excitatory-inhibitory recurrent networks

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-01-01

    An excitatory-inhibitory recurrent neuronal network is established to numerically study the effect of inhibitory neurons on the synchronization degree of neuronal systems. The obtained results show that, with the number of inhibitory neurons and the coupling strength from an inhibitory neuron to an excitatory neuron increasing, inhibitory neurons can not only reduce the synchronization degree when the synchronization degree of the excitatory population is initially higher, but also enhance it when it is initially lower. Meanwhile, inhibitory neurons could also help the neuronal networks to maintain moderate synchronized states. In this paper, we call this effect as modulation effect of inhibitory neurons. With the obtained results, it is further revealed that the ratio of excitatory neurons to inhibitory neurons being nearly 4 : 1 is an economic and affordable choice for inhibitory neurons to realize this modulation effect.

  17. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

    Directory of Open Access Journals (Sweden)

    Shivaprasad H. Venkatesha

    2014-12-01

    Full Text Available Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ, tumor necrosis factor α (TNFα, interleukin-6 (IL-6, and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA. For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis.

  18. Cytokine Response to Exercise and Its Modulation

    Directory of Open Access Journals (Sweden)

    Katsuhiko Suzuki

    2018-01-01

    Full Text Available Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

  19. CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

    Directory of Open Access Journals (Sweden)

    L. V. Matveeva

    2013-01-01

    Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

  20. Length and coverage of inhibitory decision rules

    KAUST Repository

    Alsolami, Fawaz

    2012-01-01

    Authors present algorithms for optimization of inhibitory rules relative to the length and coverage. Inhibitory rules have a relation "attribute ≠ value" on the right-hand side. The considered algorithms are based on extensions of dynamic programming. Paper contains also comparison of length and coverage of inhibitory rules constructed by a greedy algorithm and by the dynamic programming algorithm. © 2012 Springer-Verlag.

  1. Monetary rewards modulate inhibitory control

    Directory of Open Access Journals (Sweden)

    Paula Marcela Herrera

    2014-05-01

    Full Text Available The ability to override a dominant response, often referred to as behavioural inhibiton, is considered a key element of executive cognition. Poor behavioural inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioural inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/Nogo and Stop Signal Tasks. Several studies have reported a positive modulatory effect of reward on the performance of such tasks in pathological conditions such as substance abuse, pathological gambling, and ADHD. However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory paradigms are rare and consequently, little is known about the finer grained relationship between motivation and self-control. Here, we probed the effect of reward and reward magnitude on behavioural inhibition using two modified version of the widely used Stop Signal Task. The first task compared no reward with reward, whilst the other compared two different reward magnitudes. The reward magnitude effect was confirmed by the second study, whereas it was less compelling in the first study, possibly due to the effect of having no reward in some conditions. In addition, our results showed a kick start effect over global performance measures. More specifically, there was a long lasting improvement in performance throughout the task, when participants received the highest reward magnitudes at the beginning of the protocol. These results demonstrate that individuals’ behavioural inhibition capacities are dynamic not static because they are modulated by the reward magnitude and initial reward history of the task at hand.

  2. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    2001-01-01

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  3. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  4. Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

  5. Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Eliza Turlej

    2009-05-01

    Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

  6. Plasticity of cortical excitatory-inhibitory balance.

    Science.gov (United States)

    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  7. Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature

    Directory of Open Access Journals (Sweden)

    Aldag C

    2016-11-01

    Full Text Available Caroline Aldag,1,* Diana Nogueira Teixeira,1,* Phillip S Leventhal2 1Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 24Clinics, Paris, France *These authors contributed equally to this work Abstract: Skin aging is primarily due to alterations in the dermal extracellular matrix, especially a decrease in collagen I content, fragmentation of collagen fibrils, and accumulation of amorphous elastin material, also known as elastosis. Growth factors and cytokines are included in several cosmetic products intended for skin rejuvenation because of their ability to promote collagen synthesis. Matrikines and matrikine-like peptides offer the advantage of growth factor-like activities but better skin penetration due to their much smaller molecular size. In this review, we summarize the commercially available products containing growth factors, cytokines, and matrikines for which there is evidence that they promote skin rejuvenation. Keywords: cosmetics, skin, aging, growth factor, cytokine, matrikine

  8. Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

    Science.gov (United States)

    Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

    2013-01-16

    Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

  9. Cytokines: applications in domestic food animals.

    Science.gov (United States)

    Blecha, F

    1991-01-01

    Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

  10. Mimetics of Suppressor of cytokine signalling 3: novel potential therapeutics in triple breast cancer.

    Science.gov (United States)

    La Manna, Sara; Lee, Eunmi; Ouzounova, Maria; Di Natale, Concetta; Novellino, Ettore; Merlino, Antonello; Korkaya, Hasan; Marasco, Daniela

    2018-05-11

    Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumour growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex by using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA-MB-231-luci tumours as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumour growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines. This article is protected by copyright. All rights reserved. © 2018 UICC.

  11. Deficient leukemia inhibitory factor signaling in muscle precursor cells from patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Broholm, Christa; Brandt, Claus; Schultz, Ninna S

    2012-01-01

    The cytokine leukemia-inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of muscle precursor cells, an important feature of skeletal muscle maintenance and repair. We hypothesized that muscle precursor cells from patients with type 2 diabetes had a deficient response...... nor proliferation rate was affected. In conclusion, although LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic patients, LIF signaling and LIF-stimulated cell proliferation were impaired in diabetic myoblasts, suggesting a novel mechanism by which muscle function......RNA knockdown of suppressor of cytokine signaling (SOCS)3 in myoblast cultures established from healthy individuals and patients with type 2 diabetes. Myoblast proliferation rate was assessed by bromodeoxyuridine incorporation. LIF and LIFR proteins were increased in both muscle tissue and cultured myoblasts...

  12. Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

    Directory of Open Access Journals (Sweden)

    Robert Kleemann

    2010-01-01

    Full Text Available Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

  13. Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines

    International Nuclear Information System (INIS)

    Merk, Hans F.

    2005-01-01

    For all types of allergic reactions including immediate type of reactions, types II and III reactions as well as delayed-type reactions the recognition of the antigen by specifically sensitized T-lymphocytes is a prerequisite. Evidences for the key role of T-lymphocytes in the pathophysiology of allergic drug reactions are positive patch test reactions and the LTT. The proliferative response that can be measured by means of the incorporation of 3H-thymidine during DNA synthesis can be expressed as stimulation index (SI) which is the relation between the cell proliferation with antigen compared without antigen. In addition drug-specific activation of PBMC consistently resulted in IL-5 expression and secretion. The sensitivity of the LTT for the detection of drug sensitization could be improved up to 92% by the measurement of released interleukin-5. The expression and secretion of other cytokines such as IFN-γ and IL-10 was less consistently and had a diagnostic sensitivity of 36 and 50%, respectively. Microarrays are a promising new technical platform to look for better markers which can be used as a read out in the LTT and other similar assays and to study pharmacological interactions between drugs including cytokines such as interferons and the immune system

  14. Phytochemical screening and in vitro acetylcholinesterase inhibitory ...

    African Journals Online (AJOL)

    Phytochemical screening and in vitro acetylcholinesterase inhibitory activity of seven plant extracts. Titilayo Johnson, Oduje A. Akinsanmi, Enoch J. Banbilbwa, Tijani A. Yahaya, Karima Abdulaziz, Kolade Omole ...

  15. COMPARATIVE EVALUATION OF INHIBITORY ACTIVITY OF ...

    African Journals Online (AJOL)

    Osondu

    2013-02-26

    Feb 26, 2013 ... especially the four bacteria isolates used in this study are present in the epiphgram of both normal and ... Keyword: Albino snail, Archachatina marginata, Inhibitory activity, Epiphgram, Bacteria isolate. Introduction .... evolution.

  16. Cytokine production by oral and peripheral blood neutrophils in adult periodontitis.

    Science.gov (United States)

    Galbraith, G M; Hagan, C; Steed, R B; Sanders, J J; Javed, T

    1997-09-01

    Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.

  17. Evidence for an inhibitory-control theory of the reasoning brain.

    Science.gov (United States)

    Houdé, Olivier; Borst, Grégoire

    2015-01-01

    In this article, we first describe our general inhibitory-control theory and, then, we describe how we have tested its specific hypotheses on reasoning with brain imaging techniques in adults and children. The innovative part of this perspective lies in its attempt to come up with a brain-based synthesis of Jean Piaget's theory on logical algorithms and Daniel Kahneman's theory on intuitive heuristics.

  18. Macrophage migration inhibitory factor induces vascular leakage via autophagy

    Directory of Open Access Journals (Sweden)

    Hong-Ru Chen

    2015-01-01

    Full Text Available Vascular leakage is an important feature of acute inflammatory shock, which currently has no effective treatment. Macrophage migration inhibitory factor (MIF is a pro-inflammatory cytokine that can induce vascular leakage and plays an important role in the pathogenesis of shock. However, the mechanism of MIF-induced vascular leakage is still unclear. In this study, using recombinant MIF (rMIF, we demonstrated that MIF induced disorganization and degradation of junction proteins and increased the permeability of human endothelial cells in vitro. Western blotting analysis showed that rMIF treatment induced LC3 conversion and p62 degradation. Inhibition of autophagy with a PI3K inhibitor (3-MA, a ROS scavenger (NAC or autophagosomal-lysosomal fusion inhibitors (bafilomycin A1 and chloroquine rescued rMIF-induced vascular leakage, suggesting that autophagy mediates MIF-induced vascular leakage. The potential involvement of other signaling pathways was also studied using different inhibitors, and the results suggested that MIF-induced vascular leakage may occur through the ERK pathway. In conclusion, we showed that MIF triggered autophagic degradation of endothelial cells, resulting in vascular leakage. Inhibition of MIF-induced autophagy may provide therapeutic targets against vascular leakage in inflammatory shock.

  19. Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

    Science.gov (United States)

    Young, Patricia A; Morrison, Sherie L; Timmerman, John M

    2014-10-01

    The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Regulation of human cytokines by Cordyceps militaris.

    Science.gov (United States)

    Sun, Yong; Shao, Yani; Zhang, Zhiguo; Wang, Lianfen; Mariga, Alfred M; Pang, Guangchang; Geng, Chaoyu; Ho, Chi-Tang; Hu, Qiuhui; Zhao, Liyan

    2014-12-01

    Cordyceps (Cordyceps militaris) exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits). In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses) on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70), interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines. Copyright © 2014. Published by Elsevier B.V.

  1. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  2. The frontal lobes and inhibitory function

    International Nuclear Information System (INIS)

    Konishi, Seiki

    2011-01-01

    Neuropsychological studies using traditional tasks of inhibitory functions, such as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed that the frontal lobe is responsible for several types of inhibitory functions. However, the detailed psychological nature of the inhibitory functions and the precise location of their critical foci within the frontal lobe remain to be investigated. Functional magnetic resonance imaging provides spatial and temporal resolution that allowed us to illuminate at least 4 frontal regions involved in inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part of the frontal lobe in the right hemisphere was activated during response inhibition. The preSMA in the left hemisphere was activated during inhibition of proactive interference immediately after the dimension changes of the WCST. The rostral part of the frontal lobe in the left hemisphere was activated during inhibition long after the dimension changes. The dorsolateral part of the frontal lobe in the left hemisphere was activated at the dimension changes in the first time, but not in the second time. These findings provide clues to our understanding of functional differentiation of inhibitory functions and their localization in the frontal lobe. (author)

  3. Flexible brain network reconfiguration supporting inhibitory control.

    Science.gov (United States)

    Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

    2015-08-11

    The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

  4. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

  5. Proinflammatory Cytokines as Regulators of Vaginal Microbiota.

    Science.gov (United States)

    Kremleva, E A; Sgibnev, A V

    2016-11-01

    It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

  6. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  7. Organizers of inhibitory synapses come of age.

    Science.gov (United States)

    Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

    2017-08-01

    While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Bilingual Contexts Modulate the Inhibitory Control Network

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2018-03-01

    Full Text Available The present functional magnetic resonance imaging (fMRI study investigated influences of language contexts on inhibitory control and the underlying neural processes. Thirty Cantonese–Mandarin–English trilingual speakers, who were highly proficient in Cantonese (L1 and Mandarin (L2, and moderately proficient in English (L3, performed a picture-naming task in three dual-language contexts (L1-L2, L2-L3, and L1-L3. After each of the three naming tasks, participants performed a flanker task, measuring contextual effects on the inhibitory control system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3 condition, but not in the L1-L2 condition, which indicates contextual facilitation on inhibitory control performance by the L1-L2 context. Whole brain analysis of the fMRI data acquired during the flanker tasks showed more neural activations in the right prefrontal cortex and subcortical areas in the L2-L3 and L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand, suggesting greater involvement of the cognitive control areas when participants were performing the flanker task in L2-L3 and L1-L3 contexts. Effective connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for inhibitory control in the trilinguals. However, contrary to the right-lateralized network in the L1-L2 condition, functional networks for inhibitory control in the L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These findings provide a novel perspective for investigating the interaction between bilingualism (multilingualism and inhibitory control by demonstrating instant behavioral effects and neural plasticity as a function of changes in global language contexts.

  9. Invasion of human aortic endothelial cells by oral viridans group streptococci and induction of inflammatory cytokine production.

    Science.gov (United States)

    Nagata, E; de Toledo, A; Oho, T

    2011-02-01

    Oral viridans group streptococci are the major commensal bacteria of the supragingival oral biofilm and have been detected in human atheromatous plaque. Atherosclerosis involves an ongoing inflammatory response, reportedly involving chronic infection caused by multiple pathogens. The aim of this study was to examine the invasion of human aortic endothelial cells (HAECs) by oral viridans group streptococci and the subsequent cytokine production by viable invaded HAECs. The invasion of HAECs by bacteria was examined using antibiotic protection assays and was visualized by confocal scanning laser microscopy. The inhibitory effects of catalase and cytochalasin D on the invasion of HAECs were also examined. The production of cytokines by invaded or infected HAECs was determined using enzyme-linked immunosorbent assays, and a real-time polymerase chain reaction method was used to evaluate the expression of cytokine messenger RNA. The oral streptococci tested were capable of invading HAECs. The number of invasive bacteria increased with the length of the co-culture period. After a certain co-culture period, some organisms were cytotoxic to the HAECs. Catalase and cytochalasin D inhibited the invasion of HAECs by the organism. HAECs invaded by Streptococcus mutans Xc, Streptococcus gordonii DL1 (Challis), Streptococcus gordonii ATCC 10558 and Streptococcus salivarius ATCC 13419 produced more cytokine(s) (interleukin-6, interleukin-8, monocyte chemoattractant protein-1) than non-invaded HAECs. The HAECs invaded by S. mutans Xc produced the largest amounts of cytokines, and the messenger RNA expression of cytokines by invaded HAECs increased markedly compared with that by non-invaded HAECs. These results suggest that oral streptococci may participate in the pathogenesis of atherosclerosis. © 2010 John Wiley & Sons A/S.

  10. Glutamatergic clock output stimulates melatonin synthesis at night

    NARCIS (Netherlands)

    Perreau-Lenz, Stéphanie; Kalsbeek, Andries; Pévet, Paul; Buijs, Ruud M.

    2004-01-01

    The rhythm of melatonin synthesis in the rat pineal gland is under the control of the biological clock, which is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence of the SCN on melatonin synthesis, by using

  11. Current status and challenges of cytokine pharmacology

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  12. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    Objectives: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission...

  13. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...

  14. Cytokines in Sjögren's syndrome

    NARCIS (Netherlands)

    Roescher, N.; Tak, P. P.; Illei, G. G.

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the

  15. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  16. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  17. Proinflammatory cytokines in open versus laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Abu-Eshy, Saeed A.; Al-Rofaidi, Abdallah A.; Al-Faki, Ahmed S.; Ghalib, Hashim W.; Moosa, Riyadh A.; Sadik, Ali A.; Salati, Mohammad I.

    2002-01-01

    Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy. This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits. Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups. Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy. (author)

  18. Cytokines as biomarkers of nanoparticle immunotoxicity.

    Science.gov (United States)

    Elsabahy, Mahmoud; Wooley, Karen L

    2013-06-21

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.

  19. Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics

    Directory of Open Access Journals (Sweden)

    Leína Zorzanelli

    2016-01-01

    Full Text Available Background and Objective. Inflammation is central in the pathogenesis of pulmonary hypertension. We investigated how serum cytokines correlate with clinical features, hemodynamics, and lung histology in young patients with pulmonary hypertension associated with congenital cardiac shunts. Design. Prospective, observational study. Methods and Results. Patients (n=44 were aged 2.6 to 37.6 months. Group I patients (n=31 were characterized by pulmonary congestion and higher pulmonary blood flow compared to group II (p=0.022, with no need for preoperative cardiac catheterization. Group II patients (n=13 had no congestive features. At catheterization, they had elevated pulmonary vascular resistance (5.7 [4.4–7.4] Wood units·m2, geometric mean with 95% CI. Cytokines were measured by chemiluminescence. Macrophage migration inhibitory factor (MIF was found to be inversely related to pulmonary blood flow (r=-0.33, p=0.026 and was higher in group II (high pulmonary vascular resistance compared to group I (high pulmonary blood flow (p=0.017. In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted was characteristically elevated in Group I (p=0.022. Interleukin 16 was also negatively related to pulmonary blood flow (rS=-0.33, p=0.029 and was higher in patients with obstructive vasculopathy at intraoperative lung biopsy (p=0.021. Conclusion. Cytokines seem to be important and differentially regulated in subpopulations of young patients with cardiac shunts.

  20. Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

    Science.gov (United States)

    Sordillo, Peter P; Helson, Lawrence

    2015-01-01

    The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  2. Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor

    Directory of Open Access Journals (Sweden)

    Chandra Jyotsna

    2008-02-01

    Full Text Available Abstract Background We have previously shown that supernatant from Candida albicans (CA culture contains a Secretory Interleukin (IL-12 Inhibitory Factor (CA-SIIF, which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed. Results In this study, we demonstrate that the IL-12 inhibitory activity of CA-SIIF was serum-independent, based on the reduction of IL-12 levels in monocytes stimulated under serum-independent conditions. The minimal inhibitory dose of CA-SIIF was found to be 200 μg/ml. Investigation of CA-SIIF's effect on macrophages IL-12 production in vitro and in vivo also showed that CA-SIIF inhibited IL-12 production by murine macrophages both in vitro (from 571 ± 24 pg/ml to 387 ± 87 pg/ml; P = 0.05 and in vivo (from 262 ± 6 pg/ml to 144 ± 30 pg/ml; P P P P Conclusion CA-SIIF is a glycoprotein which exhibits serum-independent inhibition of IL-12 production from monocytes in vitro and in vivo, and also modulates differentiation of monocytes into dendritic cells. These results suggest important role for CA-SIIF in interactions of C. albicans with the host immune system.

  3. Correlation between enzymes inhibitory effects and antioxidant ...

    African Journals Online (AJOL)

    ... and phytochemical content of fractions was investigated. The n-butanol fraction showed significant α-glucosidase and α-amylase inhibitory effects (IC50 values 15.1 and 39.42 μg/ml, respectively) along with the remarkable antioxidant activity when compared to the other fractions. High performance liquid chromatography ...

  4. Phenotypic characterisation and assessment of the inhibitory ...

    African Journals Online (AJOL)

    Six strains of Lactobacillus spp. were isolated from fermenting corn slurry, fresh cow milk, and the faeces of pig, albino rat, and human infant. Their inhibitory action was tested against some spoilage and pathogenic bacteria. Lactobacillus acidophilus isolated from milk was found to display a higher antagonistic effect with ...

  5. Phenotypic characterisation and assessment of the inhibitory ...

    African Journals Online (AJOL)

    Fred

    inhibitory potential of Lactobacillus isolates from different sources. Oyetayo, V.O.. Department of ... Six strains of Lactobacillus spp. were isolated from fermenting corn slurry, fresh cow milk, and the faeces of pig, albino rat, and human ... the growth of some pathogens by Lactobacillus reuteri BSA 13, obtained from pig faeces.

  6. Inhibitory ability of children with developmental dyscalculia.

    Science.gov (United States)

    Zhang, Huaiying; Wu, Hanrong

    2011-02-01

    Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects. The differences of reaction time in number Stroop tasks and differences of accuracy in incongruent condition of color-word Stroop tasks and object inhibition tasks between DD-only children and their controls reached significant levels (P<0.05), and the differences of reaction time in number Stroop tasks between dyscalculic and normal children did not disappear after controlling the non-executive components. The difference of accuracy in color-word incongruent tasks between children with DD&RD and normal children reached significant levels (P<0.05). Children with DD-only confronted with general inhibitory deficits, while children with DD&RD confronted with word inhibitory deficits only.

  7. Impact of Sub-Inhibitory Concentrations of Amoxicillin on Streptococcus suis Capsule Gene Expression and Inflammatory Potential

    Directory of Open Access Journals (Sweden)

    Bruno Haas

    2016-04-01

    Full Text Available Streptococcus suis is an important swine pathogen and emerging zoonotic agent worldwide causing meningitis, endocarditis, arthritis and septicemia. Among the 29 serotypes identified to date, serotype 2 is mostly isolated from diseased pigs. Although several virulence mechanisms have been characterized in S. suis, the pathogenesis of S. suis infections remains only partially understood. This study focuses on the response of S. suis P1/7 to sub-inhibitory concentrations of amoxicillin. First, capsule expression was monitored by qRT-PCR when S. suis was cultivated in the presence of amoxicillin. Then, the pro-inflammatory potential of S. suis P1/7 culture supernatants or whole cells conditioned with amoxicillin was evaluated by monitoring the activation of the NF-κB pathway in monocytes and quantifying pro-inflammatory cytokines secreted by macrophages. It was found that amoxicillin decreased capsule expression in S. suis. Moreover, conditioning the bacterium with sub-inhibitory concentrations of amoxicillin caused an increased activation of the NF-κB pathway in monocytes following exposure to bacterial culture supernatants and to a lesser extent to whole bacterial cells. This was associated with an increased secretion of pro-inflammatory cytokines (CXCL8, IL-6, IL-1β by macrophages. This study identified a new mechanism by which S. suis may increase its inflammatory potential in the presence of sub-inhibitory concentrations of amoxicillin, a cell wall-active antibiotic, thus challenging its use for preventive treatments or as growth factor.

  8. The role of cytokine signaling in the pathogenesis of cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    abraham, Robert; Zhang, Qiang; Ødum, Niels

    2011-01-01

    Cutaneous T-cell lymphoma (CTCL) displays immunosuppressive properties and phenotypic plasticity. The malignant T cells in CTCL can possess features of immunomodulating regulatory T cells (Treg) and IL-17-producing helper T cells (Th17) depending on the stimuli they receive from antigen presenting...... therapeutic agents may potentially exploit the phenotypic plasticity of CTCL such that the malignant T cells become vulnerable to antitumor immunity....... cells and other sources. IL-2-type cytokines activate STAT5 to promote expression of Treg-related FoxP3, while various cytokines can activate STAT3 to induce synthesis of IL-10 and IL-17. When the Treg phenotype is activated in the early stages of CTCL, “immune evasion” can occur, allowing the clonal T...

  9. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  10. Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine.

    Science.gov (United States)

    McILwain, R Britt; Timpa, Joseph G; Kurundkar, Ashish R; Holt, David W; Kelly, David R; Hartman, Yolanda E; Neel, Mary Lauren; Karnatak, Rajendra K; Schelonka, Robert L; Anantharamaiah, G M; Killingsworth, Cheryl R; Maheshwari, Akhil

    2010-01-01

    Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a 'cytokine storm', leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-alpha and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have

  11. Cytokine Correlations in Youth with Tic Disorders

    Science.gov (United States)

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun

    2015-01-01

    Abstract Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Methods: Twenty-one patients, ages 4–17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=−1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=−0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders. PMID:25658821

  12. Cytokine correlations in youth with tic disorders.

    Science.gov (United States)

    Parker-Athill, E Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K

    2015-02-01

    Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Twenty-one patients, ages 4-17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=-1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=-0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

  13. Drug targets in the cytokine universe for autoimmune disease.

    Science.gov (United States)

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

    2013-03-01

    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Inhibitory coupling between inhibitory interneurons in the spinal cord dorsal horn

    Directory of Open Access Journals (Sweden)

    Ribeiro-da-Silva Alfredo

    2009-05-01

    Full Text Available Abstract Local inhibitory interneurons in the dorsal horn play an important role in the control of excitability at the segmental level and thus determine how nociceptive information is relayed to higher structures. Regulation of inhibitory interneuron activity may therefore have critical consequences on pain perception. Indeed, disinhibition of dorsal horn neuronal networks disrupts the balance between excitation and inhibition and is believed to be a key mechanism underlying different forms of pain hypersensitivity and chronic pain states. In this context, studying the source and the synaptic properties of the inhibitory inputs that the inhibitory interneurons receive is important in order to predict the impact of drug action at the network level. To address this, we studied inhibitory synaptic transmission in lamina II inhibitory interneurons identified under visual guidance in spinal slices taken from transgenic mice expressing enhanced green fluorescent protein (EGFP under the control of the GAD promoter. The majority of these cells fired tonically to a long depolarizing current pulse. Monosynaptically evoked inhibitory postsynaptic currents (eIPSCs in these cells were mediated by both GABAA and glycine receptors. Consistent with this, both GABAA and glycine receptor-mediated miniature IPSCs were recorded in all of the cells. These inhibitory inputs originated at least in part from local lamina II interneurons as verified by simultaneous recordings from pairs of EGFP+ cells. These synapses appeared to have low release probability and displayed potentiation and asynchronous release upon repeated activation. In summary, we report on a previously unexamined component of the dorsal horn circuitry that likely constitutes an essential element of the fine tuning of nociception.

  15. Synthesis, characterization and antimicrobial activity of mixed ...

    African Journals Online (AJOL)

    Synthesis, characterization and antimicrobial activity of mixed ascorbic acid - nicotinamide metal complexes. ... The result of the antimicrobial studies showed that the mixed complexes have higher inhibitory activity than the original ligands against the tested bacteria and fungi species. KEY WORDS: Ascorbic acid, ...

  16. Preschool Inhibitory Control Predicts ADHD Group Status and Inhibitory Weakness in School.

    Science.gov (United States)

    Jacobson, Lisa A; Schneider, Heather; Mahone, E Mark

    2017-12-26

    Discriminative utility of performance measures of inhibitory control was examined in preschool children with and without ADHD to determine whether performance measures added to diagnostic prediction and to prediction of informant-rated day-to-day executive function. Children ages 4-5 years (N = 105, 61% boys; 54 ADHD, medication-naïve) were assessed using performance measures (Auditory Continuous Performance Test for Preschoolers-Commission errors, Conflicting Motor Response Test, NEPSY Statue) and caregiver (parent, teacher) ratings of inhibition (Behavior Rating Inventory of Executive Function-Preschool version). Performance measures and parent and teacher reports of inhibitory control significantly and uniquely predicted ADHD group status; however, performance measures did not add to prediction of group status beyond parent reports. Performance measures did significantly predict classroom inhibitory control (teacher ratings), over and above parent reports of inhibitory control. Performance measures of inhibitory control may be adequate predictors of ADHD status and good predictors of young children's classroom inhibitory control, demonstrating utility as components of clinical assessments. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

    International Nuclear Information System (INIS)

    Mameli, Giuseppe; Astone, Vito; Khalili, Kamel; Serra, Caterina; Sawaya, Bassel E.; Dolei, Antonina

    2007-01-01

    Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFα, interferon-γ, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-β is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFα had the ability to activate the ERVWE1 promoter through an NF-κB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFα enhances the binding of the p65 subunit of NF-κB, to its cognate site within the promoter. The effect of TNFα is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFα-mediated induction of syncytin-1 in multiple sclerosis

  18. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J

    2016-01-01

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... of local, chronic islet inflammation. Since then, numerous studies have clarified how these bimodal responses depend on discrete signaling pathways. Most interest has been devoted to the proapoptotic response dependent upon mainly nuclear factor κ B and mitogen-activated protein kinase activation, leading...

  19. Progress of inflammatory cytokines in glaucoma

    Directory of Open Access Journals (Sweden)

    Ping Hu

    2015-12-01

    Full Text Available Glaucomais a group of diseases characterized by optic nerve damage and visual field defect, and pathological high intraocular pressure is a risk factor for glaucoma. Glaucoma is affected by the interaction of multiple genes and environmental factors, and inflammation may be involved in the pathogenesis of glaucoma. A great deal of studies have confirmed that high expression of connective tissue growth factor(CTGF, tumor necrosis factor-α(TNF-α, interleukins(ILs, nuclear factor-kappa B(NF-κBand various cytokines in the aqueous humor of patients with glaucoma, which have a close correlation with pathogenesis of glaucoma.This article reviews the progress of inflammatory cytokines and their relationship with glaucoma.

  20. Cytokines and the anorexia of infection: potential mechanisms and treatments.

    Science.gov (United States)

    McCarthy, D O

    2000-04-01

    Anorexia during infection is thought to be mediated by immunoregulatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the potential mechanisms of action by which these cytokines are thought to suppress food intake during infection and examines the proposition that blocking of cytokine activity might be one approach to improving food intake of the infected host.

  1. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...

  2. Screening the cytokines for diagnosis of tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    王丽豪

    2014-01-01

    Objective To select cytokines for diagnosis of tuber-culous meningitis.Methods One hundred and twenty kinds of cytokines were detected with protein chips among two tuberculous meningitis cases,two viral meningitis cases and two noninfectious neurologic disease cases.The results were compared among different disease groups to select the differential cytokines,which were

  3. Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

    Science.gov (United States)

    Djudjaj, Sonja; Lue, Hongqi; Rong, Song; Papasotiriou, Marios; Klinkhammer, Barbara M.; Zok, Stephanie; Klaener, Ole; Braun, Gerald S.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Bucala, Richard; Tittel, Andre P.; Kurts, Christian; Moeller, Marcus J.; Floege, Juergen; Ostendorf, Tammo

    2016-01-01

    Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN. PMID:26453615

  4. Cytokines in the physiopathology of depression

    OpenAIRE

    María Belén Paredes; María Eugenia Sulen

    2018-01-01

    This paper presents a bibliographical review on the relevance of the possible role of cytokines in depression. There is a consideration of the existing approaches to detection and diagnosis of depression; they are classified according to different criteria such as design methodologies and applications. Although the etiology of depression is still an issue, the focus of this paper is to highlight the various studies regarding the interactions of the immune system and brain activity linked to d...

  5. Association of Inflammatory Cytokines with Traditional and ...

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | Sep-Oct 2014 | Vol 4 ... and TNF‑α in study population were 11.7 (9.7) mg/l, 64.5 (75.2) pg/ml, and 25.3 ... cytokines also interact with various metabolic factors which are ..... European Prospective Investigation into Cancer and ... nutrition and role of one‑carbon metabolism.

  6. Cytokine Expression in Homozygous Sickle Cell Anaemia

    Directory of Open Access Journals (Sweden)

    Nnodim Johnkennedy

    2015-01-01

    Full Text Available Background: Sickle cell anaemia is an inherited disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped. The change in shape is due to the presence of an abnormal form of haemoglobin. This results in severe pain and damage to some organs. Aim and Objective: The study was carried out to determine the levels of cytokine in sickle cell anemia. Material and Methods: Thirty confirmed sickle cell patients in steady state (HbSS-SS and thirty persons with normal haemoglobin (HbAA as well as sixteen sickle cell disease in crises (HbSS-cr between the ages of 15 to 30 years were selected in this study. Cytokines including interleukin 1 beta (IL- 1β, interleukin 2 (IL- 2, interleukin (IL-6, tumour necrosis factor alpha (TNF-α, and interferon gamma (IFN- λ were measured by commercially available ELISA kits. Results: The results obtained showed that the levels of TNF-α and IL-6 in sickle cell anaemia patients in crisis were significantly elevated when compared with sickle cell in steady state (P<0.05. Similarly, the levels of IL-1β, IL-6, and IFN- λ were significantly increased in sickle cell anaemia stable state when compared to HbAA subjects (P<0.05. Conclusion: This may probably implies that cytokine imbalance is implicated in the pathogenesis of sickle cell crisis. Also, cytokines could be used as an inflammatory marker as well as related marker in disease severity and hence therapeutic intervention.

  7. Regulation and function of interleukin-36 cytokines.

    Science.gov (United States)

    Bassoy, Esen Yonca; Towne, Jennifer E; Gabay, Cem

    2018-01-01

    The interleukin (IL)-36 cytokines include 3 agonists, IL-36α, IL-36β, and IL-36γ that bind to a common receptor composed of IL-36R and IL-1RAcP to stimulate inflammatory responses. IL-36Ra is a natural antagonist that binds to IL-36R, but does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. The IL-36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  9. Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles.

    Science.gov (United States)

    Guimarães, Poliana Macedo; Scavuzzi, Bruna Miglioranza; Stadtlober, Nicole Perugini; Franchi Santos, Lorena Flor da Rosa; Lozovoy, Marcell Alysson Batisti; Iriyoda, Tatiana Mayumi Veiga; Costa, Neide Tomimura; Reiche, Edna Maria Vissoci; Maes, Michael; Dichi, Isaias; Simão, Andréa Name Colado

    2017-10-01

    The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

  10. Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on melanin synthesis.

    Science.gov (United States)

    Tokiwa, Yutaka; Kitagawa, Masaru; Raku, Takao; Yanagitani, Shusaku; Yoshino, Kenji

    2007-06-01

    Transesterification of arbutin and undecylenic acid vinyl ester was catalyzed by alkaline protease, Bioprase, in dimethylformamide to get arbutin derivative having undecylenic acid at 6-position of glucose moiety, 6-O-undecylenoyl p-hydroxyphenyl beta-D-glucopyranoside. The reaction rate increased with increase of arbutin concentration, and when its concentration was 0.9 M, the conversion rate was more than 90% under addition of 2 M undecylenic acid vinyl ester. The obtained arbutin ester significantly suppressed melanin production in murine B16 melanoma cells.

  11. Exploiting Inhibitory Siglecs to Combat Food Allergies

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0302 TITLE: Exploiting Inhibitory Siglecs to Combat Food Allergies PRINCIPAL INVESTIGATOR: Michael Kulis, Ph.D...CONTRACTING ORGANIZATION: University of North Carolina at Chapel Hill Chapel Hill, NC 27599 REPORT DATES: October 2017 TYPE OF REPORT: Annual PREPARED FOR...Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite

  12. Inhibitory Interneurons, Oxidative Stress, and Schizophrenia

    OpenAIRE

    Sullivan, Elyse M.; O’Donnell, Patricio

    2012-01-01

    Translational studies are becoming more common in schizophrenia research. The past couple of decades witnessed the emergence of novel ideas regarding schizophrenia pathophysiology that originated from both human and animal studies. The findings that glutamate and gamma-aminobutyric acid transmission are affected in the disease led to the hypothesis of altered inhibitory neurotransmission as critical for cognitive deficits and to an exploration of novel therapeutic approaches aimed at restorin...

  13. Enzyme inhibitory activity of selected Philippine plants

    International Nuclear Information System (INIS)

    Sasotona, Joseph S.; Hernandez, Christine C.

    2015-01-01

    In the Philippines, the number one cause of death are cardiovascular diseases. Diseases linked with inflammation are proliferating. This research aims to identify plant extracts that have potential activity of cholesterol-lowering, anti-hypertension, anti-gout, anti-inflammatory and fat blocker agents. Although there are commercially available drugs to treat the aforementioned illnesses, these medicine have adverse side-effects, aside from the fact that they are expensive. The results of this study will serve as added knowledge to contribute to the development of cheaper, more readily available, and effective alternative medicine. 100 plant extracts from different areas in the Philippines have been tested for potential inhibitory activity against Hydroxymethylglutaryl-coenzyme A (HMG-CoA), Lipoxygenase, and Xanthine Oxidase. The plant samples were labeled with codes and distributed to laboratories for blind testing. The effective concentration of the samples tested for Xanthine oxidase is 100 ppm. Samples number 9, 11, 14, 29, 43, 46, and 50 have shown significant inhibitory activity at 78.7%, 78.4%, 70%, 89.2%, 79%, 67.4%, and 67.5% respectively. Samples tested for Lipoxygenase inhibition were set at 33ppm. Samples number 2, 37, 901, 1202, and 1204 have shown significant inhibitory activity at 66, 84.9%, 88.55%, 93.3%, and 84.7% respectively. For HMG-CoA inhibition, the effective concentration of the samples used was 100 ppm. Samples number 1 and 10 showed significant inhibitory activity at 90.1% and 81.8% respectively. (author)

  14. Effects of hydroxysafflor yellow A on proliferation and collagen synthesis of rat vascular adventitial fibroblasts induced by angiotensin II.

    Science.gov (United States)

    Yuan, Wendan; Yang, Dongxia; Sun, Xuhong; Liu, Wei; Wang, Liang; Li, Xiaoyan; Man, Xuejing; Fu, Qiang

    2014-01-01

    1) examine the effects of hydroxysafflor yellow A (HSYA) on the proliferation, collagen and cytokine synthesis of vascular adventitial fibroblasts as induced by angiotensin II (Ang II) in normal Sprague-Dawley (SD) rats in vitro, and 2) to assess the effects of HSYA on morphological changes and collagen accumulation of vascular adventitia in spontaneously hypertensive rats (SHR) in vivo. In vitro experiment, vascular adventitial fibroblasts from SD rats were isolated, cultured, and divided into control groups, model groups and HSYA groups. Cell morphology of adventitial fibroblasts was assessed using laser confocal microscopy, while cell proliferation with the MTT assay, and collagen synthesis was determined using hydroxyproline chromatometry. Immunocytochemistry and reverse transcription PCR were used for detecting the expression of TGF-β1, MMP-1, α-SMA and NF-κB in adventitial fibroblasts. In vivo experiment, vascular adventitia proliferation and collagen synthesis were analyzed using hematoxylin-eosin and Sirius staining. Our results showed that: 1) in vitro experiment of SD rats, HSYA inhibited proliferative activity and collagen synthesis of adventitial fibroblasts as induced by Ang II, and the inhibitory effects of HSYA on the increased expression of MMP-1, TGF-β1, α-SMA and NF-κB p65 as induced by Ang II were assessed, and 2) in vivo experiment of SHR, histological analysis displayed fewer pathological changes of vascular adventitia in HSYA treatment groups as compared with no HSYA treatment groups, and MMP-1, TGF-β1, α-SMA and NF-κB p65 expression significantly reduced after HSYA treatment (P adventitia components. This study provides experimental evidence demonstrating that HSYA has the capacity to decrease vascular adventitia proliferation and hyperplasia during vascular remodeling.

  15. Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.

    Directory of Open Access Journals (Sweden)

    Bijan Raziorrouh

    Full Text Available T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB infection and the role of inhibitory molecules such as programmed death 1 (PD-1 for CD4+ T-cell failure.The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production.CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control.HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation.

  16. Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

    2013-03-15

    To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The effect of Helicobacter pylori eradication on macrophage migration inhibitory factor, C-reactive protein and fetuin-a levels

    Directory of Open Access Journals (Sweden)

    Levent Kebapcilar

    2010-06-01

    Full Text Available OBJECTIVES: To determine the effect of Helicobacter pylori (H. pylori eradication on blood levels of high-sensitivity C-reactive protein (hs-CRP, macrophage migration inhibitory factor and fetuin-A in patients with dyspepsia who are concurrently infected with H. pylori. METHODS: H.pylori infection was diagnosed based on the 14C urea breath test (UBT and histology. Lansoprazole 30 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily were given to all infected patients for 14 days; 14C UBT was then re-measured. In 30 subjects, migration inhibitory factor, fetuin-A and hs-CRP levels were examined before and after the eradication of H. pylori infection and compared to levels in 30 healthy subjects who tested negative for H. pylori infection. RESULTS: Age and sex distribution were comparable between patients and controls. Migration inhibitory factor and hs-CRP levels were higher, and fetuin-A levels were lower, in H. pylori-infected patients (p0.05. CONCLUSION: These findings suggest that H. pylori eradication reduces the levels of pro-inflammatory cytokines such as migration inhibitory factor and hs-CRP and also results in a significant increase in anti-inflammatory markers such as fetuin-A.

  18. Regulation of cytokines by small RNAs during skin inflammation

    Directory of Open Access Journals (Sweden)

    Mikkelsen Jacob G

    2010-07-01

    Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

  19. Selective LXRα inhibitory effects observed in plant extracts of MEH184 (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica)

    International Nuclear Information System (INIS)

    Kim, Kang Ho; Choi, Seung Hyun; Lee, Thomas S.; Oh, Won Keun; Kim, Dong Sun; Kim, Jae Bum

    2006-01-01

    Liver X receptors (LXRs) are nuclear hormone receptors that behave as lipid sensors of cellular cholesterol and fatty acid. Although LXR activation can alleviate hypercholesterolemia by inducing cholesterol efflux, it also results in undesirable effects of fatty acid synthesis, resulting in hepatic steatosis and hyperlipidemia. Therefore, it is critical to identify LXRα inhibitory agents that would repress fatty acid synthesis and hepatic lipid accumulation. In current study, screening of plant extracts used for traditional oriental medicine resulted in the identification of two candidates demonstrating selective LXRα inhibitory activity. These were whole leaf methanol extracts of Parthenocissua tricuspidata (MEH184) and Euscaphis japonica (MEH185). Both MEH184 and MEH185 decreased transcriptional activity of LXRα and the expression of LXRα target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184 significantly reduced lipogenesis and adipocyte differentiation. Together, the data imply that MEH184 and MEH185 possess selective antagonistic properties on LXRα to downregulate lipogenesis

  20. Three-dimensional structure and cytokine distribution of platelet-rich fibrin.

    Science.gov (United States)

    Bai, Meng-Yi; Wang, Ching-Wei; Wang, Jyun-Yi; Lin, Ming-Fang; Chan, Wing P

    2017-02-01

    Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

  1. Three-dimensional structure and cytokine distribution of platelet-rich fibrin

    Directory of Open Access Journals (Sweden)

    Meng-Yi Bai

    Full Text Available OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1 can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg; it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5 to low at the plasma end (p=0.19. Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

  2. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7.

    Science.gov (United States)

    Jorjão, Adeline Lacerda; de Oliveira, Felipe Eduardo; Leão, Mariella Vieira Pereira; Carvalho, Cláudio Antonio Talge; Jorge, Antonio Olavo Cardoso; de Oliveira, Luciane Dias

    2015-01-01

    This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-12) by mouse macrophages (RAW 264.7). Three microorganism preparations were used: live L. rhamnosus (LLR) suspension, heat-killed L. rhamnosus (HKLR) suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR) suspension, which were cultured with macrophages (37°C, 5% CO2) for 2 h and 30 min. After that, cells were cultured for 16 h. The supernatants were used for the quantitation of cytokines, by ELISA. The results were compared with the synthesis induced by lipopolysaccharide (LPS) and analysed, using ANOVA and Tukey test, 5%. LLR and HKLR groups were able to significantly increase the production of TNF-α, IL-6, and IL-10 (P 0.05). All the L. rhamnosus suspensions were not able to produce detectable levels of IL-1β or significant levels of IL-4 and IL-12 (P > 0.05). In conclusion, live and heat-killed L. rhamnosus suspensions were able to induce the synthesis of different cytokines with proinflammatory (TNF-α and IL-6) or regulatory (IL-10) functions, suggesting the role of strain L. rhamnosus ATCC 7469 in the modulation or in the stimulation of immune responses.

  3. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7

    Directory of Open Access Journals (Sweden)

    Adeline Lacerda Jorjão

    2015-01-01

    Full Text Available This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-12 by mouse macrophages (RAW 264.7. Three microorganism preparations were used: live L. rhamnosus (LLR suspension, heat-killed L. rhamnosus (HKLR suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR suspension, which were cultured with macrophages (37°C, 5% CO2 for 2 h and 30 min. After that, cells were cultured for 16 h. The supernatants were used for the quantitation of cytokines, by ELISA. The results were compared with the synthesis induced by lipopolysaccharide (LPS and analysed, using ANOVA and Tukey test, 5%. LLR and HKLR groups were able to significantly increase the production of TNF-α, IL-6, and IL-10 (P0.05. All the L. rhamnosus suspensions were not able to produce detectable levels of IL-1β or significant levels of IL-4 and IL-12 (P>0.05. In conclusion, live and heat-killed L. rhamnosus suspensions were able to induce the synthesis of different cytokines with proinflammatory (TNF-α and IL-6 or regulatory (IL-10 functions, suggesting the role of strain L. rhamnosus ATCC 7469 in the modulation or in the stimulation of immune responses.

  4. Cytokine profile and pathology in human leishmaniasis

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    Ribeiro-de-Jesus A.

    1998-01-01

    Full Text Available The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-g is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-g production and high IL-4 and IL-10 levels (Th2 cytokines are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC. Moreover, IL-12 restores IFN-g production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-g production, since anti-IL-10 monoclonal antibody (mAb restores in vitro IFN-g production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-g are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-g levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml. This response was restored by IL-12 (308 ± 342 pg/ml and anti-IL-10 mAb (380 ± 245 pg/ml (P<0.05. Later during the disease, high levels of IFN-g and TNF-a are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-a levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02. Although production of IFN-g and TNF-a might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis

  5. Cytokines in the modulation of eosinophilia

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    Faccioli Lúcia H

    1997-01-01

    Full Text Available In this review we discuss our recently results showing interleukin 5 (IL-5 involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

  6. [Membrane-bound cytokine and feedforward regulation].

    Science.gov (United States)

    Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua

    2013-10-01

    Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

  7. Original paper Cytokine profiles in axial spondyloarthritis

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    Marta Madej

    2015-04-01

    Full Text Available Objectives: Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA. In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. Material and methods: Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient’s medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS, the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. Results : In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively. Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001 was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295. No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. Conclusions : We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may

  8. Hypothyroidism and depression: Are cytokines the link?

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    Parimal S Tayde

    2017-01-01

    Full Text Available Context: Primary hypothyroidism has been thought of as an inflammatory condition characterized by raised levels of cytokines such as C-reactive protein (CRP, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α. Depression is also well known to occur in hypothyroidism. Depression is also characterized by elevated inflammatory cytokines. We planned to study whether cytokines play an important part in linking these two conditions. Objectives: (1 To know the prevalence of depression in overt hypothyroidism due to autoimmune thyroid disease. (2 To correlate the levels of inflammatory markers with the occurrence of depression. (3 To study the effect of levothyroxine on inflammatory markers and depression. Materials and Methods: In this longitudinal, case–controlled study, 33 patients with autoimmune hypothyroidism (thyroid-stimulating hormone >10 uIU/ml were included with 33 age-, sex-, and body max index-matched healthy controls. Individuals were tested for Serum TNF-α, IL-6, high-sensitivity-CRP (hs-CRP. They were assessed for depression using Montgomery Asberg Depression Rating Scale (MADRS and World Health Organization Quality of Life (QOL Scale. Patients received L Thyroxine titrated to achieve euthyroidism and were reassessed for inflammatory markers and cognitive dysfunction. Results: Nineteen patients (57% had mild to moderate depression (MADRS >11. After 6 months of treatment, eight patients (42% had remission of depression with significant improvement in QOL scores (P < 0.05. TNF-α, IL-6, and hs-CRP were significantly elevated in patients compared with controls and reduced with therapy but did not reach baseline as controls. The change in inflammatory markers correlated with improvement in QOL scores in social and environmental domains (P < 0.01. Conclusions: Primary autoimmune hypothyroidism is an inflammatory state characterized by elevated cytokines which decline with LT4 therapy. It is associated with depression and poor

  9. From cytokines to pragmatic designs: changing paradigms.

    Science.gov (United States)

    Heddle, Nancy M

    2017-10-01

    Emily Cooley was a well-respected medical technologist and morphologist with a remarkable skill set. She was highly regarded both professionally and personally. The "Emily Cooley Lectureship and Award" was established to honor her in particular and medical technologists in general. This article first reviews how a medical laboratory technologist was inspired to become a clinical researcher, then goes on to describe research that led to the discovery of cytokines as the cause of febrile nonhemolytic transfusion and the use of a pragmatic randomized controlled trial design to address evidence of harm when stored red blood cells were transfused. Important lessons for performing quality, meaningful research are highlighted. © 2017 AABB.

  10. Inhibitory neurotransmission and olfactory memory in honeybees.

    Science.gov (United States)

    El Hassani, Abdessalam Kacimi; Giurfa, Martin; Gauthier, Monique; Armengaud, Catherine

    2008-11-01

    In insects, gamma-aminobutyric acid (GABA) and glutamate mediate fast inhibitory neurotransmission through ligand-gated chloride channel receptors. Both GABA and glutamate have been identified in the olfactory circuit of the honeybee. Here we investigated the role of inhibitory transmission mediated by GABA and glutamate-gated chloride channels (GluCls) in olfactory learning and memory in honeybees. We combined olfactory conditioning with injection of ivermectin, an agonist of GluCl receptors. We also injected a blocker of glutamate transporters (L-trans-PDC) or a GABA analog (TACA). We measured acquisition and retention 1, 24 and 48 h after the last acquisition trial. A low dose of ivermectin (0.01 ng/bee) impaired long-term olfactory memory (48 h) while a higher dose (0.05 ng/bee) had no effect. Double injections of ivermectin and L-trans-PDC or TACA had different effects on memory retention, depending on the doses and agents combined. When the low dose of ivermectin was injected after Ringer, long-term memory was again impaired (48 h). Such an effect was rescued by injection of both TACA and L-trans-PDC. A combination of the higher dose of ivermectin and TACA decreased retention at 48 h. We interpret these results as reflecting the involvement of both GluCl and GABA receptors in the impairment of olfactory long-term memory induced by ivermectin. These results illustrate the diversity of inhibitory transmission and its implication in long-term olfactory memory in honeybees.

  11. Leukemia inhibitory factor in rat fetal lung development: expression and functional studies.

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    Cristina Nogueira-Silva

    Full Text Available BACKGROUND: Leukemia inhibitory factor (LIF and interleukin-6 (IL-6 are members of the family of the glycoprotein 130 (gp130-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. METHODOLOGY/PRINCIPAL FINDINGS: LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. CONCLUSIONS/SIGNIFICANCE: The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.

  12. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

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    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  13. Mucorales spores induce a proinflammatory cytokine response in human mononuclear phagocytes and harbor no rodlet hydrophobins.

    Science.gov (United States)

    Wurster, Sebastian; Thielen, Vanessa; Weis, Philipp; Walther, Paul; Elias, Johannes; Waaga-Gasser, Ana Maria; Dragan, Mariola; Dandekar, Thomas; Einsele, Hermann; Löffler, Jürgen; Ullmann, Andrew J

    2017-11-17

    Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.

  14. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

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    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  15. Interplay of cytokines in preterm birth

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    Monika Pandey

    2017-01-01

    Full Text Available Preterm infants (i.e., born before <37 wk of gestation are at increased risk of morbidity and mortality and long-term disabilities. Global prevalence of preterm birth (PTB varies from 5 to 18 per cent. There are multiple aetiological causes and factors associated with PTB. Intrapartum infections are conventionally associated with PTB. However, maternal genotype modulates response to these infections. This review highlights the association of cytokine gene polymorphisms and their levels with PTB. Varying PTB rates across the different ethnic groups may be as a result of genetically mediated varying cytokines response to infections. Studies on genetic variations in tumour necrosis factor-alpha, interleukin-1 alpha (IL-1α, IL-1β, IL-6, IL-10 and toll-like receptor-4 genes and their association with PTB, have been reviewed. No single polymorphism of the studied genes was found to be associated with PTB. However, increased maternal levels of IL-1β and IL-6 and low levels of IL-10 have been found to be associated with PTB.

  16. Angiogenic Factors and Cytokines in Diabetic Retinopathy

    Science.gov (United States)

    Abcouwer, Steven F.

    2013-01-01

    Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DR-associated vascular dysfunction, edema and angiogenesis. This has stimulated research of alternative therapeutic targets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored. PMID:24319628

  17. An evolutionary scenario for gonadotrophin-inhibitory hormone in chordates.

    Science.gov (United States)

    Osugi, T; Ubuka, T; Tsutsui, K

    2015-06-01

    In 2000, we discovered a novel hypothalamic neuropeptide that actively inhibits gonadotrophin release in quail and termed it gonadotrophin-inhibitory hormone (GnIH). GnIH peptides have subsequently been identified in most representative species of gnathostomes. They all share a C-terminal LPXRFamide (X = L or Q) motif. GnIH can inhibit gonadotrophin synthesis and release by decreasing the activity of GnRH neuroes, as well as by directly inhibiting pituitary gonadotrophin secretion in birds and mammals. To investigate the evolutionary origin of GnIH and its ancestral function, we identified a GnIH precursor gene encoding GnIHs from the brain of sea lamprey, the most ancient lineage of vertebrates. Lamprey GnIHs possess a C-terminal PQRFamide motif. In vivo administration of one of lamprey GnIHs stimulated the expression of lamprey GnRH in the hypothalamus and gonadotophin β mRNA in the pituitary. Thus, GnIH may have emerged in agnathans as a stimulatory neuropeptide that subsequently diverged to an inhibitory neuropeptide during the course of evolution from basal vertebrates to later-evolved vertebrates, such as birds and mammals. From a structural point of view, pain modulatory neuropeptides, such as neuropeptide FF (NPFF) and neuropeptide AF, share a C-terminal PQRFamide motif. Because agnathans possess both GnIH and NPFF genes, the origin of GnIH and NPFF genes may date back before the emergence of agnathans. More recently, we identified a novel gene encoding RFamide peptides in the amphioxus. Molecular phylogenetic analysis and synteny analysis indicated that this gene is closely related to the genes of GnIH and NPFF of vertebrates. The results suggest that the identified protochordate gene is similar to the common ancestor of GnIH and NPFF genes, indicating that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. The GnIH and NPFF genes may have diverged by whole-genome duplication during the course of vertebrate

  18. Aldose reductase inhibitory compounds from Xanthium strumarium.

    Science.gov (United States)

    Yoon, Ha Na; Lee, Min Young; Kim, Jin-Kyu; Suh, Hong-Won; Lim, Soon Sung

    2013-09-01

    As part of our ongoing search for natural sources of therapeutic and preventive agents for diabetic complications, we evaluated the inhibitory effects of components of the fruit of Xanthium strumarium (X. strumarium) on aldose reductase (AR) and galactitol formation in rat lenses with high levels of glucose. To identify the bioactive components of X. strumarium, 7 caffeoylquinic acids and 3 phenolic compounds were isolated and their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with published data. The abilities of 10 X. strumarium-derived components to counteract diabetic complications were investigated by means of inhibitory assays with rat lens AR (rAR) and recombinant human AR (rhAR). From the 10 isolated compounds, methyl-3,5-di-O-caffeoylquinate showed the most potent inhibition, with IC₅₀ values of 0.30 and 0.67 μM for rAR and rhAR, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate, methyl-3,5-di-O-caffeoylquinate showed competitive inhibition of rhAR. Furthermore, methyl-3,5-di-O-caffeoylquinate inhibited galactitol formation in the rat lens and in erythrocytes incubated with a high concentration of glucose, indicating that this compound may be effective in preventing diabetic complications.

  19. Rational decision-making in inhibitory control.

    Science.gov (United States)

    Shenoy, Pradeep; Yu, Angela J

    2011-01-01

    An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability.

  20. When is an Inhibitory Synapse Effective?

    Science.gov (United States)

    Qian, Ning; Sejnowski, Terrence J.

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl^- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl^- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl^-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K^+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K^+ through GABA_B receptors.

  1. Rational Decision-Making in Inhibitory Control

    Science.gov (United States)

    Shenoy, Pradeep; Yu, Angela J.

    2011-01-01

    An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability. PMID:21647306

  2. Comparison of Heuristics for Inhibitory Rule Optimization

    KAUST Repository

    Alsolami, Fawaz

    2014-09-13

    Knowledge representation and extraction are very important tasks in data mining. In this work, we proposed a variety of rule-based greedy algorithms that able to obtain knowledge contained in a given dataset as a series of inhibitory rules containing an expression “attribute ≠ value” on the right-hand side. The main goal of this paper is to determine based on rule characteristics, rule length and coverage, whether the proposed rule heuristics are statistically significantly different or not; if so, we aim to identify the best performing rule heuristics for minimization of rule length and maximization of rule coverage. Friedman test with Nemenyi post-hoc are used to compare the greedy algorithms statistically against each other for length and coverage. The experiments are carried out on real datasets from UCI Machine Learning Repository. For leading heuristics, the constructed rules are compared with optimal ones obtained based on dynamic programming approach. The results seem to be promising for the best heuristics: the average relative difference between length (coverage) of constructed and optimal rules is at most 2.27% (7%, respectively). Furthermore, the quality of classifiers based on sets of inhibitory rules constructed by the considered heuristics are compared against each other, and the results show that the three best heuristics from the point of view classification accuracy coincides with the three well-performed heuristics from the point of view of rule length minimization.

  3. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    Science.gov (United States)

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is

  4. Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Yoon, Tae-Jin [Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju (Korea, Republic of); Lee, Young Ho [Department of Anatomy, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lee, Jeung-Hoon, E-mail: jhoon@cnu.ac.kr [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Skin Med Company, Daejeon (Korea, Republic of)

    2015-04-17

    Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal.

  5. Overview of Macrophage Migration Inhibitory Factor (MIF as a Potential Biomarker Relevant to Adiposity

    Directory of Open Access Journals (Sweden)

    Jun Nishihira

    2012-07-01

    Full Text Available The cytokine “macrophage migration inhibitory factor (MIF” is generally recognized as a proinflammatory cytokine, and MIF is involved in broad range of acute and chronic inflammatory states. With regard to glucose metabolism and insulin secretion, MIF is produced by pancreatic β cells and acts as a positive regulator of insulin secretion. In contrast, it is evident that MIF expressed in adipose tissues causes insulin resistance. Concerning MIF gene analysis, we found four alleles: 5-, 6-, 7-and 8-CATT at position −794 of MIF gene in a Japanese population. Genotypes without the 5-CATT allele were more common in the obese subjects than in the lean or overweight groups. It is conceivable that promoter polymorphism in the MIF gene is profoundly linked with obesity relevant to lifestyle diseases, such as diabetes. Obesity has become a serious social issue due to the inappropriate nutritional balance, and the consumption of functional foods (including functional foods to reduce fat mass is expected to overcome this issue. In this context, MIF would be a reliable quantitative biomarker to evaluate the effects of functional foods on adiposity.

  6. The Role of Macrophage Migration Inhibitory Factor (MIF) in Ultraviolet Radiation-Induced Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Tadamichi [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, 930-0194, Toyama (Japan)

    2010-08-09

    Ultraviolet (UV) radiation is the most common cause of physical injury to the skin due to environmental damage, and UV exposure substantially increases the risk of actinic damage to the skin. The inflammatory changes induced by acute UV exposure include erythema (sunburn) of the skin, while chronic exposure to solar UV radiation causes photo-aging, immunosuppression, and ultimately, carcinogenesis of the skin. After skin damage by UV radiation, the cells are known to secrete many cytokines, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α. and macrophage migration inhibitory factor (MIF). MIF was originally identified as a lymphokine that concentrates macrophages at inflammatory loci, and is known to be a potent activator of macrophages in vivo. MIF is considered to play an important role in cell-mediated immunity. Since the molecular cloning of MIF cDNA, MIF has been re-evaluated as a proinflammatory cytokine and pituitary-derived hormone that potentiates endotoxemia. MIF is ubiquitously expressed in various tissues, including the skin. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. This article reviews the latest findings on the roles of MIF with regard to UV-induced skin cancer.

  7. Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

    International Nuclear Information System (INIS)

    Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki; Yoon, Tae-Jin; Lee, Young Ho; Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-01-01

    Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal

  8. The Role of Macrophage Migration Inhibitory Factor (MIF) in Ultraviolet Radiation-Induced Carcinogenesis

    International Nuclear Information System (INIS)

    Shimizu, Tadamichi

    2010-01-01

    Ultraviolet (UV) radiation is the most common cause of physical injury to the skin due to environmental damage, and UV exposure substantially increases the risk of actinic damage to the skin. The inflammatory changes induced by acute UV exposure include erythema (sunburn) of the skin, while chronic exposure to solar UV radiation causes photo-aging, immunosuppression, and ultimately, carcinogenesis of the skin. After skin damage by UV radiation, the cells are known to secrete many cytokines, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α. and macrophage migration inhibitory factor (MIF). MIF was originally identified as a lymphokine that concentrates macrophages at inflammatory loci, and is known to be a potent activator of macrophages in vivo. MIF is considered to play an important role in cell-mediated immunity. Since the molecular cloning of MIF cDNA, MIF has been re-evaluated as a proinflammatory cytokine and pituitary-derived hormone that potentiates endotoxemia. MIF is ubiquitously expressed in various tissues, including the skin. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. This article reviews the latest findings on the roles of MIF with regard to UV-induced skin cancer

  9. The Role of Macrophage Migration Inhibitory Factor (MIF in Ultraviolet Radiation-Induced Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tadamichi Shimizu

    2010-08-01

    Full Text Available Ultraviolet (UV radiation is the most common cause of physical injury to the skin due to environmental damage, and UV exposure substantially increases the risk of actinic damage to the skin. The inflammatory changes induced by acute UV exposure include erythema (sunburn of the skin, while chronic exposure to solar UV radiation causes photo-aging, immunosuppression, and ultimately, carcinogenesis of the skin. After skin damage by UV radiation, the cells are known to secrete many cytokines, including interleukin (IL-1, IL-6, tumor necrosis factor (TNF-α. and macrophage migration inhibitory factor (MIF. MIF was originally identified as a lymphokine that concentrates macrophages at inflammatory loci, and is known to be a potent activator of macrophages in vivo. MIF is considered to play an important role in cell-mediated immunity. Since the molecular cloning of MIF cDNA, MIF has been re-evaluated as a proinflammatory cytokine and pituitary-derived hormone that potentiates endotoxemia. MIF is ubiquitously expressed in various tissues, including the skin. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. This article reviews the latest findings on the roles of MIF with regard to UV-induced skin cancer.

  10. Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Finucane, Orla M

    2012-11-01

    High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

  11. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    Science.gov (United States)

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (pvitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  12. Reduced Fc∊RI-Mediated Release of Asthma-Promoting Cytokines and Chemokines from Human Basophils during Omalizumab Therapy

    Science.gov (United States)

    Oliver, Janet M.; Tarleton, Christy A.; Gilmartin, Laura; Archibeque, Tereassa; Qualls, Clifford R.; Diehl, Lorena; Wilson, Bridget S.; Schuyler, Mark

    2010-01-01

    Background Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair®), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, Fc∊RI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the Fc∊RI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined. Methods Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests. Results Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release. Conclusions Omalizumab may reduce asthma symptoms in part by suppressing the Fc∊RI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of Fc∊RI caused by omalizumab treatment. PMID:19844128

  13. Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

    LENUS (Irish Health Repository)

    Nic An Ultaigh, Sinead

    2011-02-23

    Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1\\/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg\\/ml), an anti-TLR2 antibody (OPN301, 1 μg\\/ml) or an immunoglobulin G (IgG) (1 μg\\/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

  14. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Directory of Open Access Journals (Sweden)

    Masaru Takeuchi

    Full Text Available Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM, 26 patients with idiopathic macular hole (MH, and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  15. Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

    Science.gov (United States)

    Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

    2017-12-15

    The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.

    Science.gov (United States)

    Kanegi, R; Hatoya, S; Tsujimoto, Y; Takenaka, S; Nishimura, T; Wijewardana, V; Sugiura, K; Takahashi, M; Kawate, N; Tamada, H; Inaba, T

    2016-07-15

    Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P Feline LIF will further improve reproduction and stem cell research in the feline family. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Identification and isolation of the cyclooxygenase-2 inhibitory principle in Isatis tinctoria.

    Science.gov (United States)

    Danz, H; Stoyanova, S; Wippich, P; Brattström, A; Hamburger, M

    2001-07-01

    Various extracts prepared from the traditional dye and medicinal plant Isatis tinctoria L. were submitted to a broad in vitro screening against 16 anti-inflammatory targets. Dichloromethane (DCM) extracts from dried leaves showed a marked cyclooxygenase (COX) inhibitory activity with a preferential effect on COX-2 catalysed prostaglandin synthesis. A supercritical fluid extraction (SFE) procedure employing CO2-modifier mixtures was developed by which the bioactivity profile and chromatographic fingerprint of the DCM extract could be reproduced. High-resolution activity directed on-line identification of the COX-2 inhibitory principle, using a combination of LC-DAD-MS with a microtitre-based bioassay, led to the identification of tryptanthrin (1) as the constituent responsible for essentially all COX-2 inhibitory activity in the crude extract. Following on-line identification, 1 was isolated at preparative scale and its structure confirmed by comparison with synthetic tryptanthrin. In an assay with lipopolysaccharide stimulated Mono Mac 6 cells, tryptanthrin (1) was of comparable potency (IC50 = 64 nM) than the preferential COX-2 inhibitors nimesulide (IC50 = 39 nM) and NS 398 (IC50 = 2 nM). The SFE extract and 1 showed no cytotoxicity in Mono Mac 6 and RAW 264.7 cells when tested at 100 microg/ml and 10 microM, respectively.

  18. Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells.

    Science.gov (United States)

    Yan, Jun; Mitra, Abhisek; Hu, Jiemiao; Cutrera, Jeffery J; Xia, Xueqing; Doetschman, Thomas; Gagea, Mihai; Mishra, Lopa; Li, Shulin

    2016-05-01

    Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death. Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice. Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise, deficiency in IL-10 or NKT cells abolished the protective role of IL-30 against sepsis. Furthermore, IL-30 induced IL-10 production in purified and LPS-stimulated NKT cells. Blocking IL-6R or gp130 inhibited IL-30 mediated IL-10 production. IL-30 is important in modulating production of NKT cytokines and subsequent NKT cell-mediated immune regulation of other cells. Therefore, IL-30 has a role in prevention and treatment of sepsis via modulation of cytokine production by NKT. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Cytokine genes as potential biomarkers for muscle weakness in OPMD

    DEFF Research Database (Denmark)

    Riaz, Muhammad; Raz, Yotam; van der Slujis, Barbara

    2016-01-01

    is a dominant, late-onset myopathy, caused by an alanine-expansion mutation in the gene encoding for poly(A) binding protein nuclear 1 (expPABPN1). Here, we investigated the hypothesis that cytokines could mark OPMD disease state. We determined cytokines levels the vastus lateralis muscle from genetically...... confirmed expPABPN1 carriers at a symptomatic or a presymptomatic stage. We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing exp PABPN1 Six cytokines were found to be consistently down-regulated in OPMD vastus lateralis muscles. Expression levels...

  20. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Hansen, Morten Bagge

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo......Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations...

  1. Inflammatory cytokines and immune system modulation by aerobic ...

    African Journals Online (AJOL)

    Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging. ... Physical exercise is effective in reducing (or ameliorate) the ..... moderate resistance training program increases muscle .... Nutrition Metabo-.

  2. Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus.

    Science.gov (United States)

    Acharya, Anirudh B; Thakur, Srinath; Muddapur, M V; Kulkarni, Raghavendra D

    Chronic periodontitis may influence systemic cytokines in type 2 diabetes. This study aimed to evaluate the cytokine ratios in type 2 diabetes with, and without chronic periodontitis. Gingival status, periodontal, glycemic parameters and serum cytokines were evaluated in participants grouped as healthy, chronic periodontitis, and type 2 diabetes with, and without chronic periodontitis. Cytokine ratios showed significant differences in type 2 diabetes and chronic periodontitis, were highest in participants having both type 2 diabetes and chronic periodontitis, with a statistically significant cut-off point and area under curve by receiver operating characteristic. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  4. Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-12-01

    Full Text Available Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

  5. Cytokines and Angiogenesis in the Corpus Luteum

    Directory of Open Access Journals (Sweden)

    António M. Galvão

    2013-01-01

    Full Text Available In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL, regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced cytokines, such as tumor necrosis factor α (TNF, interferon gamma (IFNG, or Fas ligand (FASL, pointed out their role on angiogenic activity modulation throughout the luteal phase. Thus, the main purpose of this review is to highlight the interaction between immune, endothelial, and luteal steroidogenic cells, regarding vascular dynamics/changes during establishment and regression of the equine CL.

  6. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    Science.gov (United States)

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

  7. Timing control by redundant inhibitory neuronal circuits

    Energy Technology Data Exchange (ETDEWEB)

    Tristan, I., E-mail: itristan@ucsd.edu; Rulkov, N. F.; Huerta, R.; Rabinovich, M. [BioCircuits Institute, University of California, San Diego, La Jolla, California 92093-0402 (United States)

    2014-03-15

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.

  8. A recombinant wheat serpin with inhibitory activity

    DEFF Research Database (Denmark)

    Rasmussen, Søren K; Dahl, Søren Weis; Nørgård, Anette

    1996-01-01

    A full-length clone encoding the wheat (Triticum aestivum L.) serpin WSZ1 was isolated from a cDNA library based on mRNA from immature grain. The 398 amino acid sequence deduced from the cDNA was corroborated by sequencing CNBr peptides of WSZ1 purified from resting grain. WSZ1 belongs to the sub......A full-length clone encoding the wheat (Triticum aestivum L.) serpin WSZ1 was isolated from a cDNA library based on mRNA from immature grain. The 398 amino acid sequence deduced from the cDNA was corroborated by sequencing CNBr peptides of WSZ1 purified from resting grain. WSZ1 belongs...... sequencing indicated that only few serpins are encoded by wheat, but at least three distinct genes are expressed in the grain. Cleavage experiments on a chymotrypsin column suggested a Gln-Gln reactive site bond not previously observed in inhibitory serpins....

  9. Comparison of Heuristics for Inhibitory Rule Optimization

    KAUST Repository

    Alsolami, Fawaz; Chikalov, Igor; Moshkov, Mikhail

    2014-01-01

    Friedman test with Nemenyi post-hoc are used to compare the greedy algorithms statistically against each other for length and coverage. The experiments are carried out on real datasets from UCI Machine Learning Repository. For leading heuristics, the constructed rules are compared with optimal ones obtained based on dynamic programming approach. The results seem to be promising for the best heuristics: the average relative difference between length (coverage) of constructed and optimal rules is at most 2.27% (7%, respectively). Furthermore, the quality of classifiers based on sets of inhibitory rules constructed by the considered heuristics are compared against each other, and the results show that the three best heuristics from the point of view classification accuracy coincides with the three well-performed heuristics from the point of view of rule length minimization.

  10. Impaired inhibitory control in recreational cocaine users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed.

  11. Serum trypsin inhibitory capacity in hemodialysis patients

    International Nuclear Information System (INIS)

    Hashemi, Mohammad; Mehrabifar, Hamid; Homayooni, Fatemeh; Naderi, Mohammad; Montazerifar, Farzaneh; Ghavami, Saeid

    2009-01-01

    It has been established that overproduction of reactive oxygen species (ROS) occurs during hemodialysis causing oxidation of proteins. Alpha-1-antitrypsin is the major circulating anti-protease which contains methionine in the active site. The aim of the present study was to measure the level of serum trypsin inhibitory capacity (sTIC) in hemodialysis patients. This case-control study was performed in 52 hemodialysis patients and 49 healthy controls. sTIC was measured by enzymatic assay. The sTIC was significantly (P< 0.001) lower in hemodialysis patients (1.87 + - 0.67 micron mol/min/mL) than healthy controls (2.83 + - 0.44 micron mol/min/L). Reduction of sTIC may be due to the oxidation of methionine residue in the reactive site of alpha-1 antitrypsin. (author)

  12. Timing control by redundant inhibitory neuronal circuits

    International Nuclear Information System (INIS)

    Tristan, I.; Rulkov, N. F.; Huerta, R.; Rabinovich, M.

    2014-01-01

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model

  13. The biochemical anatomy of cortical inhibitory synapses.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Heller

    Full Text Available Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain.

  14. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  15. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Science.gov (United States)

    Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  16. Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

    Science.gov (United States)

    Castro, J E Z; Vado-Solis, I; Perez-Osorio, C; Fredeking, T M

    2011-01-01

    Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

  17. Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation.

    Science.gov (United States)

    Radtke, Simone; Wüller, Stefan; Yang, Xiang-ping; Lippok, Barbara E; Mütze, Barbara; Mais, Christine; de Leur, Hildegard Schmitz-Van; Bode, Johannes G; Gaestel, Matthias; Heinrich, Peter C; Behrmann, Iris; Schaper, Fred; Hermanns, Heike M

    2010-03-15

    The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known to crosstalk on multiple levels, for instance by regulating the mRNA stability of targeted cytokines through activation of the p38-MAPK pathway. In our study we discovered a new mechanism that answers the long-standing question how pro-inflammatory cytokines and environmental stress restrict immediate signalling of interleukin (IL)-6-type cytokines. We show that p38, activated by IL-1beta, TNFalpha or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation. We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130. Consequently, inhibition of p38 or MK2, deletion of MK2 or mutation of crucial amino acids within the MK2 target site or the di-leucine internalisation motif blocks receptor depletion and restores IL-6-dependent STAT activation as well as gene induction. Hence, a novel negative crosstalk mechanism for cytokine signalling is described, where cytokine receptor turnover is regulated in trans by pro-inflammatory cytokines and stress stimuli to coordinate the inflammatory response.

  18. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    Science.gov (United States)

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Withaferin A Associated Differential Regulation of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Seema Dubey

    2018-02-01

    Full Text Available A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA. Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β, CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1β and IL-18. These data suggest that dietary agent WFA concurrently targets NF-κB and the inflammasome complex, leading to inhibition of IL-1β and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

  20. Mixed ligand complexes of Cu(II)/Zn(II) ions containing (m-)/(p-) carboxylato phenyl azo pentane 2,4-dione and 2,2‧-bipyridine/1,10 phenanthroline: Synthesis, characterization, DNA binding, nuclease and topoisomerase I inhibitory activity

    Science.gov (United States)

    Hasan, Md. Amin; Kumari, Niraj; Singh, Kanhaiya; Singh, Kiran; Mishra, Lallan

    2016-01-01

    Metal complexes of type [Cu(L1H)2(bpy)] (1), [Zn(L1H)2(bpy)] (2), [Cu(L2H)2(bpy)] (3) and [Cu(L2H)2(Phen)] (4) (L1H2 = 3-[N‧-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, L2H2 = 4-[N‧-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, bpy = 2,2‧-bipyridine, Phen = 1,10 phenanthroline) are synthesized and characterized using spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, electronic absorption and emission) and elemental analysis data. The assembly of the complexes involving intramolecular H-bonding is displayed using corresponding crystal structure. Binding of the complexes separately with Calf Thymus DNA is monitored using UV-vis spectral titrations. The displacement of ethidium bromide (EB) bound to DNA by the complexes, in phosphate buffer solution (pH ∼ 7.2) is monitored using fluorescence spectral titrations. Nuclease activity of the complexes follow the order 4 > 3 > 1 > 2. The gel electrophoretic mobility assay measurement in presence of minor groove binder 4‧,6-diamidino-2-phenylindole (DAPI), suggests that complexes preferably bind with the minor groove of DNA. Topoisomerase I inhibitory activity of the complexes 3 and 4 inhibit topoisomerase I activity with IC50 values of 112 and 87 μM respectively.

  1. Mixed ligand complexes of Cu(II)/Zn(II) ions containing (m-)/(p-) carboxylato phenyl azo pentane 2,4-dione and 2,2'-bipyridine/1,10 phenanthroline: Synthesis, characterization, DNA binding, nuclease and topoisomerase I inhibitory activity.

    Science.gov (United States)

    Hasan, Md Amin; Kumari, Niraj; Singh, Kanhaiya; Singh, Kiran; Mishra, Lallan

    2016-01-05

    Metal complexes of type [Cu(L1H)2(bpy)] (1), [Zn(L1H)2(bpy)] (2), [Cu(L2H)2(bpy)] (3) and [Cu(L2H)2(Phen)] (4) (L1H2=3-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, L2H2=4-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, bpy=2,2'-bipyridine, Phen=1,10 phenanthroline) are synthesized and characterized using spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, electronic absorption and emission) and elemental analysis data. The assembly of the complexes involving intramolecular H-bonding is displayed using corresponding crystal structure. Binding of the complexes separately with Calf Thymus DNA is monitored using UV-vis spectral titrations. The displacement of ethidium bromide (EB) bound to DNA by the complexes, in phosphate buffer solution (pH∼7.2) is monitored using fluorescence spectral titrations. Nuclease activity of the complexes follow the order 4>3>1>2. The gel electrophoretic mobility assay measurement in presence of minor groove binder 4',6-diamidino-2-phenylindole (DAPI), suggests that complexes preferably bind with the minor groove of DNA. Topoisomerase I inhibitory activity of the complexes 3 and 4 inhibit topoisomerase I activity with IC50 values of 112 and 87μM respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models

    Directory of Open Access Journals (Sweden)

    Cheryl L Gatto

    2010-06-01

    Full Text Available Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS, the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states.

  3. Albumin synthesis in protein energy malnutrition

    International Nuclear Information System (INIS)

    Duggan, C.; Hardy, S.; Kleinman, R.E.; Lembcke, J.; Young, V.E.

    1994-01-01

    The dietary treatment of protein-energy malnutrition (PEM) has been designed on an empirical basis, with outcomes for successful management including body weight gain and resolution of apathy. We propose using the measurements of protein synthesis as a more objective measure of renourishment. We will therefore randomize a group of malnourished children (weigh-for-height Z score 13 C-leucine and serial measurements of 13 C-enrichment of albumin. Isotope infusions will be performed on days one and three, following a standard three hour fast. Since albumin synthesis is reduced under the influence of cytokines which mediate the inflammatory response, results will be stratified according to the presence or absence of clinically apparent infections. We hypothesize that the provision of added dietary protein will optimize albumin synthesis rates in PEM as well as attenuate the reduction in albumin synthesis seen in the presence of infections. (author). 20 refs

  4. Plasticity of regulatory T cells under cytokine pressure.

    Science.gov (United States)

    Diaconu, Carmen C; Neagu, Ana I; Lungu, Răzvan; Tardei, Graţiela; Alexiu, Irina; Bleotu, Coralia; Economescu, Mihaela Chivu; Bumbăcea, Roxana S; Pele, Irina; Bumbăcea, Dragoş

    2010-01-01

    CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

  5. Modulation of cytokine production profiles in splenic dendritic cells ...

    African Journals Online (AJOL)

    We examined the role of splenic dendritic cells in immune response to Toxoplasma gondii infection in SAG1 (P30+) transgenic mice by investigating the kinetics of intracellular cytokines expression of IL-4, IL-10, IL-12 and IFN-γ by intracellular cytokine staining (ICS) using flow cytometry, and compared the results to those of ...

  6. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

  7. Peripheral parasitaemia and its association with plasma cytokines ...

    African Journals Online (AJOL)

    Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. Results: The results revealed a mean parasite density of ...

  8. Anti-cytokine therapies in T1D

    DEFF Research Database (Denmark)

    Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

    2013-01-01

    Therapeutic targeting of proinflammatory cytokines is clinically beneficial in several autoimmune disorders. Several of these cytokines are directly implicated in the pathogenesis of type 1 diabetes, suggesting opportunities for design of clinical trials in type 1 diabetes that incorporate select...... suitable for modulating the immune response in T1D....

  9. Cytokines and chemokines involved in acute retinal necrosis

    NARCIS (Netherlands)

    L. De Visser (Lenneke); J.H. de Boer (Joke); G.T. Rijkers; Wiertz, K. (Karin); H.J. van den Ham; de Boer, R. (Rob); van Loon, A.M. (Anton M.); A. Rothová (Aniki); J.D.F. de Groot-Mijnes (Jolanda )

    2017-01-01

    textabstractPURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients

  10. Demystifying the cytokine network: Mathematical models point the way.

    Science.gov (United States)

    Morel, Penelope A; Lee, Robin E C; Faeder, James R

    2017-10-01

    Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Serum triiodothyronine levels and inflammatory cytokine production capacity

    NARCIS (Netherlands)

    Rozing, Maarten P.; Westendorp, Rudi G J; Maier, Andrea B.; Wijsman, Carolien A.; Frölich, Marijke; De Craen, Anton J M; Van Heemst, Diana

    Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual

  12. Inflammatory cytokines and risk of coronary heart disease

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Gao, Pei

    2014-01-01

    Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta...

  13. Cytokines and Chemokines Involved in Acute Retinal Necrosis

    NARCIS (Netherlands)

    de Visser, Lenneke; H de Boer, Joke; T Rijkers, Ger; Wiertz, Karin; van den Ham, Henk-Jan; de Boer, Rob; M van Loon, Anton; Rothova, Aniki; de Groot-Mijnes, Jolanda D F

    2017-01-01

    Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were

  14. Cytokines and the neurodevelopmental basis of mental illness

    Directory of Open Access Journals (Sweden)

    Udani eRatnayake

    2013-10-01

    Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

  15. Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

    Directory of Open Access Journals (Sweden)

    Peleg Rider

    2016-01-01

    Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

  16. Multiparameter fluorescence imaging for quantification of TH-1 and TH-2 cytokines at the single-cell level

    Science.gov (United States)

    Fekkar, Hakim; Benbernou, N.; Esnault, S.; Shin, H. C.; Guenounou, Moncef

    1998-04-01

    Immune responses are strongly influenced by the cytokines following antigenic stimulation. Distinct cytokine-producing T cell subsets are well known to play a major role in immune responses and to be differentially regulated during immunological disorders, although the characterization and quantification of the TH-1/TH-2 cytokine pattern in T cells remained not clearly defined. Expression of cytokines by T lymphocytes is a highly balanced process, involving stimulatory and inhibitory intracellular signaling pathways. The aim of this study was (1) to quantify the cytokine expression in T cells at the single cell level using optical imaging, (2) and to analyze the influence of cyclic AMP- dependent signal transduction pathway in the balance between the TH-1 and TH-2 cytokine profile. We attempted to study several cytokines (IL-2, IFN-(gamma) , IL-4, IL-10 and IL-13) in peripheral blood mononuclear cells. Cells were prestimulated in vitro using phytohemagglutinin and phorbol ester for 36h, and then further cultured for 8h in the presence of monensin. Cells were permeabilized and then simple-, double- or triple-labeled with the corresponding specific fluorescent monoclonal antibodies. The cell phenotype was also determined by analyzing the expression of each of CD4, CD8, CD45RO and CD45RA with the cytokine expression. Conventional images of cells were recorded with a Peltier- cooled CCD camera (B/W C5985, Hamamatsu photonics) through an inverted microscope equipped with epi-fluorescence (Diaphot 300, Nikon). Images were digitalized using an acquisition video interface (Oculus TCX Coreco) in 762 by 570 pixels coded in 8 bits (256 gray levels), and analyzed thereafter in an IBM PC computer based on an intel pentium processor with an adequate software (Visilog 4, Noesis). The first image processing step is the extraction of cell areas using an edge detection and a binary thresholding method. In order to reduce the background noise of fluorescence, we performed an opening

  17. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  18. The inflammatory cytokines: molecular biomarkers for major depressive disorder?

    Science.gov (United States)

    Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

    2015-01-01

    Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

  19. Citoquinas en tuberculosis Cytokines in tuberculosis

    Directory of Open Access Journals (Sweden)

    Jaime I. Rodríguez

    1997-04-01

    Full Text Available La tuberculosis continúa siendo un modelo inmunológico para estudiar las infecciones intracelulares. Entenderlos complejos mecanismos de interacción de la micobacteria con el sistema inmune del hospedero permitirá un manejo más racional de los fenómenos clínicos que se presentan en la enfermedad. Las citoquinas desempeñan un papel fundamental tanto en el desarrollo de los mecanismos de inmunidad protectora como en el daño tisular presente en esta enfermedad. La estimulación in vitro de linfocitos de sujetos sanos tuberculino positivos con antígenos específicos induce preferencial mente un patrón de citoquinas tipo I (1'IL-2, 1'IFN-y, ~IL-4, ~IL-5, mientras que en la mayoría de los pacientes no se presenta este patrón. Las citoquinas tipo I conducen a la activación de los macrófagos que a su vez inhiben la replicación de las micobacterias. En el ratón, los macrófagos activados inhiben la micobacteria por medio del óxido nítrico; en los humanos la producción de óxido nítrico por los macrófagos no está plenamente demostrada. Recientemente se ha demostrado que la infección con M. tuberculosis puede inducir apoptosis en los macrófagos infectados. La apoptosis depende de la producción del Factor de Necrosis Tumoral a y de óxido nítrico. Paradójicamente, ellipoarabinomanán manosilado (ManLAM presente en la pared de las micobacterias inhibe la apoptosis. Estos hallazgos muestran un nuevo fenómeno en la interacción micobacteriamacrófago el cual debe estar finamente regulado tanto en el microorganismo como en el hospedero. Tuberculosis continues to be a model to study the immunological aspects of intracellular infections. A better understanding of the mycobacteria.host interaction would allow a more rational approach to the clinical problems of this disease. Cytokines playa key role in the development of protective immunity as well as in the tissue injury that occurs during the disease. In vitro stimulation with

  20. Comparative phytochemical and growth inhibitory studies on the leaf ...

    African Journals Online (AJOL)

    Comparative phytochemical and growth inhibitory studies on the leaf and root bark extracts of securinega Virosa (roxb ex. Willd) baill ... The growth inhibitory tests were carried out between 1-30 mg/ in a period of 24-96 h while the phytochemical screening was carried out on the plant parts using standard methods. At 24 h ...

  1. Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool

    Science.gov (United States)

    Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.

    2015-01-01

    Research Findings: The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children…

  2. Inhibitory Synaptic Plasticity - Spike timing dependence and putative network function.

    Directory of Open Access Journals (Sweden)

    Tim P Vogels

    2013-07-01

    Full Text Available While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical □ndings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

  3. Optimization of inhibitory decision rules relative to length and coverage

    KAUST Repository

    Alsolami, Fawaz; Chikalov, Igor; Moshkov, Mikhail; Zielosko, Beata

    2012-01-01

    The paper is devoted to the study of algorithms for optimization of inhibitory rules relative to the length and coverage. In contrast with usual rules that have on the right-hand side a relation "attribute ≠ value", inhibitory rules have a relation

  4. Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine

    2016-01-01

    -IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...

  5. Inhibitory effect of cyanide on wastewater nitrification ...

    Science.gov (United States)

    The effect of CN- (CN-) on nitrification was examined with samples from nitrifying wastewater enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN- used in the batch assays were 0.03, 0.06, 0.1 and 1.0 mg/L. There was considerable decrease in SOUR with increasing dosages of CN-. A decrease of more than 50% in nitrification activity was observed at 0.1 mg/L CN-. Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN- dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric heme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. Nitrification is the first step of nitrogen removal is wastewater, and it is susceptible to inhibition by many industrial chemical. We looked at

  6. Angiogenesis is inhibitory for mammalian digit regeneration

    Science.gov (United States)

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration. PMID:27499862

  7. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease.

    Science.gov (United States)

    Stallmach, T; Hebisch, G; Joller-Jemelka, H I; Orban, P; Schwaller, J; Engelmann, M

    1995-09-01

    A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood. The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8. In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed. Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine

  8. Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.

    Science.gov (United States)

    Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

    2011-11-23

    The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.

  9. Early human pregnancy serum cytokine levels predict autoimmunity in offspring.

    Science.gov (United States)

    Lindehammer, Sabina Resic; Björck, Sara; Lynch, Kristian; Brundin, Charlotte; Marsal, Karel; Agardh, Daniel; Fex, Malin

    2011-09-01

    It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNFα, IFNγ, IL-2, IL-1β and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.

  10. Synthesis and characterization of 4-[(E)-(-2,5 ...

    African Journals Online (AJOL)

    The synthesis of 4-[(E)-(-2,5- dimethoxybenzylidene)amino] benzoic acid. Schiff base, SBDAB was carried out inorder to determine its inhibitory efficiency at higher temperature using weight loss and gasometric techniques. The results showed that the inhibition efficiency of the studied Schiff base increased with increase in ...

  11. Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade

    Directory of Open Access Journals (Sweden)

    Richa Tyagi

    2015-02-01

    Full Text Available Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress, the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis by enhancing the phosphorylation of eIF2α by protein kinase-like ER kinase (PERK. Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.

  12. IL-36 cytokines in autoimmunity and inflammatory disease.

    Science.gov (United States)

    Ding, Liping; Wang, Xiaohui; Hong, Xiaoping; Lu, Liwei; Liu, Dongzhou

    2018-01-05

    The inteleukin-36 (IL-36) cytokines include IL-36α, IL-36β, IL-36γ and IL-36Ra, which belong to the IL-1 family and exert pro-inflammatory effects on various target cells such as keratinocytes, synoviocytes, dendritic cells and T cells. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory diseases. Here, we provide a brief review on the activation of IL-36 family cytokines and their involvement in autoimmunity and inflammatory diseases, which will provide further insights in understanding the functions of IL-36 family cytokines in the pathophysiology of autoimmunity and inflammatory diseases.

  13. Organic synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, S.E.

    1991-01-01

    This paper reports on reactions of organoboranes. Organoboron routes to unsaturated hydrocarbons. Boronic ester homologation. Properties of organosilicon compounds. Alkene synthesis (Peterson olefination). Allylsilanes and acylsilanes.

  14. Studies on protein synthesis by protoplasts of Saccharomyces carlsbergensis I. The effect of ribonuclease on protein synthesis

    NARCIS (Netherlands)

    Kloet, S.R. de; Wermeskerken, R.K.A. van; Koningsberger, V.V.

    1961-01-01

    Ribonuclease was found to inhibit the protein synthesis in the naked yeast protoplast for nearly 100%. Even small concentrations (5 μg/ml) were found inhibitory. The cause of this inhibition can be attributed at least in part to a 90% inhibition of the respiration. Amino acid uptake was found to

  15. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

    Directory of Open Access Journals (Sweden)

    Weber Friedemann

    2006-03-01

    Full Text Available Abstract Background SARS coronavirus (SARS-CoV is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. Results A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. Conclusion Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

  16. Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family.

    Science.gov (United States)

    Elson, G C; Graber, P; Losberger, C; Herren, S; Gretener, D; Menoud, L N; Wells, T N; Kosco-Vilbois, M H; Gauchat, J F

    1998-08-01

    In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the soluble form of the IL-6R alpha-chain, or a subunit of a multimeric cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.

  17. Inhibitory effects of antimicrobial agents against Fusarium species.

    Science.gov (United States)

    Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko

    2015-08-01

    We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 μg/ml of tobramycin and 25 μg/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed. © The Author 2015. Published by Oxford University Press on

  18. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kristi Alnek

    Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  19. IL-2 absorption affects IFN-gamma and IL-5, but not IL-4 producing memory T cells in double color cytokine ELISPOT assays.

    Science.gov (United States)

    Quast, Stefan; Zhang, Wenji; Shive, Carey; Kovalovski, Damian; Ott, Patrick A; Herzog, Bernhard A; Boehm, Bernhard O; Tary-Lehmann, Magdalena; Karulin, Alexey Y; Lehmann, Paul V

    2005-09-01

    Cytokine assays are gaining increasing importance for human immune monitoring because they reliably detect antigen-specific T cells in primary PBMC, even at low clonal sizes. Double color ELISPOT assays permit the simultaneous visualization of cells producing two different cytokines. Permitting the simultaneous assessment of type 1 and 2 immunity and due to the limited numbers of PBMC available from human study subjects, double color assays should be particularly attractive for clinical trials. Since the performance of double color assays has not yet been validated, we set out to compare them to single color measurements. Testing the recall antigen-induced cytokine response of PBMC, we found that double color assays regularly provided lower numbers of IFN-gamma and IL-5 spots than single color measurements when IL-2 detection was part of the double color assay. We showed that the inhibitory effect resulted from IL-2 absorption and could be overcome by either antibody free preactivation cultures or by inclusion of anti-CD28 antibody. In contrast, the simultaneous detection of IL-2 did not affect the numbers of IL-4 spots. Therefore, unlike IL-2/IL-4 and IFN-gamma/IL-5 assays, IL-2/IFN-gamma, and IL-2/IL-5 assays require compensation for the IL-2 capture to provide accurate numbers for the frequencies of cytokine producing memory T cells.

  20. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7

    OpenAIRE

    Jorj?o, Adeline Lacerda; de Oliveira, Felipe Eduardo; Le?o, Mariella Vieira Pereira; Carvalho, Cl?udio Antonio Talge; Jorge, Antonio Olavo Cardoso; de Oliveira, Luciane Dias

    2015-01-01

    This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-?, IL-1?, IL-4, IL-6, IL-10, and IL-12) by mouse macrophages (RAW 264.7). Three microorganism preparations were used: live L. rhamnosus (LLR) suspension, heat-killed L. rhamnosus (HKLR) suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR) suspension, which were cultured with macrophages (37?C, 5% CO2) for 2?h and 30?min. After that, cells were cul...

  1. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder

    Institute of Scientific and Technical Information of China (English)

    Anne Masi; Nicholas Glozier; Russell Dale; Adam J.Guastella

    2017-01-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark.Investigations of immune system problems in ASD,including aberrations in cytokine profiles and signaling,have been increasing in recent times and are the subject of ongoing interest.With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD,or function as an objective measure of response to treatment,this review summarizes the role of the immune system,discusses the relationship between the immune system,the brain,and behavior,and presents previouslyidentified immune system abnormalities in ASD,specifically addressing the role of cytokines in these aberrations.The roles and identification of biomarkers are also addressed,particularly with respect to cytokine profiles in ASD.

  2. Influence of phthalates on cytokine production in monocytes and macrophages

    DEFF Research Database (Denmark)

    Hansen, Juliana Frohnert; Bendtzen, Klaus; Boas, Malene

    2015-01-01

    BACKGROUND: Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which......://www.crd.york.ac.uk/NIHR_PROSPERO, registration number CRD42013004236). In vivo, ex vivo and in vitro studies investigating the influence of phthalates on cytokine mRNA expression and cytokine secretion in animals and humans were included. A total of 11 reports, containing 12 studies, were found eligible for inclusion. In these, a total of four...... different phthalate diesters, six primary metabolites (phthalate monoesters) and seven different cytokines were investigated. Though all studies varied greatly in study design and species sources, four out of five studies that investigated di-2-ethylhexyl phthalate found an increased tumour necrosis factor...

  3. Impact of weight loss on oxidative stress and inflammatory cytokines ...

    African Journals Online (AJOL)

    diet regimen, where as the control group received medical treatment only for 12 weeks. Results: The mean values of ... Keywords: Type 2 diabetes, weight reduction, oxidative stress, cytokines, obesity. ..... muscle in severely obese subjects.

  4. Cytokines in bipolar disorder vs. healthy control subjects

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Braüner, Julie Vestergaard; Kessing, Lars Vedel

    2013-01-01

    Bipolar disorder may be associated with peripheral immune system dysfunction; however, results in individual studies are conflicting. Our aim was to systematically review evidence of peripheral cytokine alterations in bipolar disorder integrating findings from various affective states....

  5. Characterization and antagonism of cytokine-induced eosinophil priming

    NARCIS (Netherlands)

    Rosas Rosas, Ana Marcela

    2006-01-01

    Allergic asthma is an inflammatory disease characterized by bronchial hyper-responsiveness, airway inflammation, and reversible obstruction of the airways. In humans, cytokine activated eosinophils are thought to be important players in this process since they can release inflammatory mediators

  6. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

    Science.gov (United States)

    Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

    2017-04-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

  7. Cytokines in Gaucher disease: Role in the pathogenesis of bone ...

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    2015-03-03

    Mar 3, 2015 ... The impact of therapy on bone manifestations of Gaucher disease . ... types: classical or alternative, depending on the predominant cytokine in the .... avascular necrosis, bone infarcts and localised cortical thin- ning may be ...

  8. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma.

    Science.gov (United States)

    Vuolo, Francieli; Petronilho, Fabricia; Sonai, Beatriz; Ritter, Cristiane; Hallak, Jaime E C; Zuardi, Antonio Waldo; Crippa, José A; Dal-Pizzol, Felipe

    2015-01-01

    Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

  9. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Directory of Open Access Journals (Sweden)

    Francieli Vuolo

    2015-01-01

    Full Text Available Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA. In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p. and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

  10. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Science.gov (United States)

    Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

    2013-01-01

    Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

  11. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  12. Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

    Directory of Open Access Journals (Sweden)

    Denise Silveira-Lemos

    2013-01-01

    Full Text Available Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group before and after praziquantel treatment (ACT-TR group. Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA, increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

  13. Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis

    Science.gov (United States)

    Savva, Athina; Brouwer, Matthijs C.; Valls Serón, Mercedes; Le Roy, Didier; Ferwerda, Bart; van der Ende, Arie; Bochud, Pierre-Yves; van de Beek, Diederik; Calandra, Thierry

    2016-01-01

    Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (−794 CATT5–8; rs5844572) and a single-nucleotide polymorphism (−173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and −173 C high-expression MIF alleles were associated with unfavorable outcome (P = 0.005 and 0.003) and death (P = 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P = 0.02] and carriage of the CATT7 allele (OR 5.12, P = 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P = 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy. PMID:26976591

  14. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    International Nuclear Information System (INIS)

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung; Kwon, Taeg Kyu; Shin, Tae-Yong; Park, Pil-Hoon; Lee, Seung-Ho; Kim, Sang-Hyun

    2014-01-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H 1 receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases

  15. Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

    Science.gov (United States)

    Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam

    2006-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544

  16. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Shin, Tae-Yong [College of Pharmacy, Woosuk University, Jeonju 565-701 (Korea, Republic of); Park, Pil-Hoon; Lee, Seung-Ho [College of Pharmacy, Youngnam University, Kyungsan 712-749 (Korea, Republic of); Kim, Sang-Hyun, E-mail: shkim72@knu.ac.kr [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2014-02-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.

  17. Inhibitory effects of bee venom on mast cell-mediated allergic inflammatory responses.

    Science.gov (United States)

    Kang, Yun-Mi; Chung, Kyung-Sook; Kook, In-Hoon; Kook, Yoon-Bum; Bae, Hyunsu; Lee, Minho; An, Hyo-Jin

    2018-06-01

    Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune‑associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC‑1 cells were treated with BV prior to stimulation with phorbol‑12‑myristate 13‑acetate plus calcium ionophore A23187 (PMACI). The production of allergy‑associated pro‑inflammatory mediators was examined, and the underlying mechanisms were investigated. Furthermore, to investigate whether BV exhibits anti‑inflammatory effects associated with anti‑allergic effects in vivo, a compound 48/80‑induced anaphylaxis model was used. BV inhibited histamine release, mRNA expression and production of cytokines in the PMACI‑stimulated HMC‑1 cells. Furthermore, the inhibitory effects of BV on mitogen‑activated protein kinase (MAPK), MAPK kinase, signal transducer and activator of transcription 3 (STAT3) and Akt were demonstrated. The present study also investigated the ability of BV to inhibit compound 48/80‑induced systemic anaphylaxis in vivo. BV protected the mice against compound 48/80‑induced anaphylactic‑associated mortality. Furthermore, BV suppressed the mRNA expression levels of pro‑inflammatory cytokines, and suppressed the activation of MAPK and STAT3 in this model. These results provide novel insights into the possible role of BV as a modulator for mast cell‑mediated allergic inflammatory disorders.

  18. Relationship between cytokines and running economy in marathon runners

    Directory of Open Access Journals (Sweden)

    Luna Junior Luiz Antonio

    2016-01-01

    Full Text Available Running economy (RE, expresses the relationship between the energy cost of running (Cr and the work performed by a runner and is an predictor of performance. Given the intense effort of marathon runners during training and competition and the dearth of studies that address performance and cytokines in this population, the objective of the current study was to investigate the relationship between RE and cytokines in marathon runners.

  19. Photoperiodic Regulation of Behavioral Responsiveness to Proinflammatory Cytokines

    OpenAIRE

    Wen, Jarvi C.; Prendergast, Brian J.

    2007-01-01

    Symptoms of bacterial infection include decreases in body mass (cachexia), induction of depressive-like hedonic tone (anhedonia), decreases in food intake (anorexia), and increases in body temperature (fever). Recognition of bacteria by the innate immune system triggers the release of proinflammatory cytokines which induce these sickness behaviors via central and peripheral substrates. In Siberian hamsters, exposure to short day lengths decreases both the production of proinflammatory cytokin...

  20. Human astrocytes: secretome profiles of cytokines and chemokines.

    Directory of Open Access Journals (Sweden)

    Sung S Choi

    Full Text Available Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1, IL-6, IL-8 (CXCL8, MCP-1 (CCL2, MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10, MIP-1α (CCL3 and RANTES (CCL5, in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.

  1. Measuring histamine and cytokine release from basophils and mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

    2014-01-01

    Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ...... skin mast cells. We also give an example of an activation protocol for basophil and mast cell cytokine release and discuss approaches for cytokine detection....

  2. OPG/RANKL/RANK cytokine system in renal osteodystrophy

    Directory of Open Access Journals (Sweden)

    Ivica Avberšek-Lužnik

    2007-11-01

    consequently its serum levels.Conclusions: Our results support the outcomes of in vitro studies of PTH inhibitory action on OPG and PTH stimulatory action on RANKL synthesis. The highest OPG values were observed in the first tertile and RANKL levels in the third PTH tertile. In HD patients with high bone turnover, PTH action leads to disbalance in OPG/RANKL/RANK and consequently to accelerated bone resorption. We proved the role of the OPG/RANKL/RANK system in the pathogenesis of renal osteodystrophy.

  3. Simplified Method to Produce Human Bioactive Leukemia Inhibitory Factor in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Houman Kahroba

    2016-07-01

    Full Text Available Background Human leukemia inhibitory factor (hLIF is a poly functional cytokine with numerous regulatory effects on different cells. Main application of hLIF is maintaining pluripotency of embryonic stem cells. hLIF indicated effective work in implantation rate of fertilized eggs and multiple sclerosis (MS treatment. Low production of hLIF in eukaryotic cells and prokaryotic host’s problems for human protein production convinced us to develop a simple way to reach high amount of this widely used clinical and research factor. Objectives In this study we want to purify recombinant human leukemia inhibitory factor in single simple method. Materials and Methods This is an experimental study, gene expression: human LIF gene was codon optimized for expression in Escherichia coli and attached his-tag tail to make it extractable. After construction and transformation of vector to E. coli, isopropyl β-D-1-thiogalactopyranoside (IPTG used for induction. Single step immobilized metal affinity chromatography (IMAC used for purification confirmed by Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE and western blotting. Bioactivity of the hLIF were tested by MTT assay with TF-1 cells and CISH gene stimulation in monocyte and TF-1 by real-time PCR. Induction by 0.4 mM of IPTG in 25°C for 3 hours indicated best result for soluble expression. SPSS indicated P ˂ 0.05 that is significant for our work. Results Cloning, expression, and extraction of bio active rhLIF was successfully achieved according MTT assay and real time PCR after treatment of TF-1 and monocyte cell lines. Conclusions We developed an effective single step purification method to produce bioactive recombinant hLIF in E. coli. For the first time we used CISH gene stimulating for bioactivity test for qualifying of recombinant hLIF for application.

  4. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

    Science.gov (United States)

    Twu, Olivia; Dessí, Daniele; Vu, Anh; Mercer, Frances; Stevens, Grant C; de Miguel, Natalia; Rappelli, Paola; Cocco, Anna Rita; Clubb, Robert T; Fiori, Pier Luigi; Johnson, Patricia J

    2014-06-03

    The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

  5. INVESTIGATION OF CYTOKINE PROFILE IN PATIENTS WITH REACTIVE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T. V. Gaponova

    2008-01-01

    Full Text Available Abstract. Pathogenesis of reactive arthritis (ReA is not clear yet. Several trials suggest that increased production of proinflammatory cytokines is responsible for development of arthritis in ReA, while other studies report that Th1 cytokine response in ReA is impaired in favor of Th2 response. The aim of our study was to investigate serum levels of cytokines IL-1β, IL-4, IL-6, TNFα, IFNγ and IL-1Ra in the patients with ReA of different etiology, as compared with infection-related arthritis. The results of our study had demonstrated that serum levels of IL-1β and TNFα in the patients with ReA were significantly higher, whereas IL-1Ra, IL-4, IL-6 proved to be significantly lower than in healthy controls. Serum levels of IL-6 were significantly higher in patients with chronic ReA, as compared to the cases of acute and recurrent ReA. No significant differences in cytokine profiles were found between the patients with ReA, and the persons with infection-related arthritis. The data obtained are, generally, suggestive for proinflammatory Th1 cytokine profile in ReA patients studied, this confirming the mostly assumed pathogenetic hypothesis for reactive arthritis where an underlying cytokine imbalance is suggested. (Med. Immunol., 2008, vol. 10, N 2-3, pp 167-172.

  6. Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Can Zhang

    Full Text Available Painful neuropathy (PN is a prevalent condition in patients with metabolic syndrome (MetS. However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN remain unclear. In the current study, high-fat-fed mice (HF mice were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF-α, and interleukin (IL-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

  7. Developmental and Functional Control of Natural Killer Cells by Cytokines

    Directory of Open Access Journals (Sweden)

    Yang Wu

    2017-08-01

    Full Text Available Natural killer (NK cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tissues. The development and functions of such NK cells are controlled by various cytokines, such as fms-like tyrosine kinase 3 ligand (FL, kit ligand (KL, interleukin (IL-3, IL-10, IL-12, IL-18, transforming growth factor-β, and common-γ chain family cytokines, which operate at different stages by regulating distinct signaling pathways. Nevertheless, the specific roles of each cytokine that regulates NK cell development or that shapes different NK cell functions remain unclear. In this review, we attempt to describe the characteristics of each cytokine and the existing protocols to expand NK cells using different combinations of cytokines and feeder cells. A comprehensive understanding of the role of cytokines in NK cell development and function will aid the generation of better efficacy for adoptive NK cell treatment.

  8. New ACE-Inhibitory Peptides from Hemp Seed (Cannabis sativa L.) Proteins.

    Science.gov (United States)

    Orio, Lara P; Boschin, Giovanna; Recca, Teresa; Morelli, Carlo F; Ragona, Laura; Francescato, Pierangelo; Arnoldi, Anna; Speranza, Giovanna

    2017-12-06

    A hemp seed protein isolate, prepared from defatted hemp seed meals by alkaline solubilization/acid precipitation, was subjected to extensive chemical hydrolysis under acid conditions (6 M HCl). The resulting hydrolysate was fractionated by semipreparative RP-HPLC, and the purified fractions were tested as inhibitors of angiotensin converting enzyme (ACE). Mono- and bidimensional NMR experiments and LC-MS analyses led to the identification of four potentially bioactive peptides, i.e. GVLY, IEE, LGV, and RVR. They were prepared by solid-phase synthesis, and tested for ACE-inhibitory activity. The IC 50 values were GVLY 16 ± 1.5 μM, LGV 145 ± 13 μM, and RVR 526 ± 33 μM, confirming that hemp seed may be a valuable source of hypotensive peptides.

  9. In vitro evaluation of inhibitory effect of Phoenix dactylifera bark ...

    African Journals Online (AJOL)

    investigate its in vitro inhibitory effects on lipid peroxidation in the brain, liver, and kidney tissues of rat, ... diseases associated with lipid peroxidation such as cancers and Alzheimer's disease, but further studies ... the family Arecaceae.

  10. Macrophage migration inhibitory factor and autism spectrum disorders

    NARCIS (Netherlands)

    Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard

    OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes

  11. 2-(2-Pyridyl) Benzimidazole Analogs and their beta-Glucuronidase Inhibitory Activity

    International Nuclear Information System (INIS)

    Kamil, A.; Noureen, S.

    2015-01-01

    Synthesis of 2-(2-Pyridyl) benzimidazole analogs 1-11 have been carried out and evaluated for in vitro beta-glucuronidase inhibitory potential. The compounds 4 (IC/sub 50/ = 4.06 ± 0.34 meuM), 5 (IC/sub 50/ = 09.63 ± 0.81 meuM), 1 (IC/sub 50/ = 19.66 ± 0.44 meuM), 7 (IC/sub 50/ = 24.75 ± 0.25 meuM), 6 (IC/sub 50/ = 26.30 ± 1.37 meuM), and 3 (IC/sub 50/ = 32.11 ± 0.89 meuM), showed beta-glucuronidase inhibitory activity superior to the standard D-saccharic acid 1,4-lactone, with (IC/sub 50/ = 48.4 ± 1.25 meuM). Based on structure-activity relationship, we discover a new class of potent beta-glucuronidase inhibitors. (author)

  12. Aggressive Periodontitis and Chronic Arthritis: Blood Mononuclear Cell Gene Expression and Plasma Protein Levels of Cytokines and Cytokine Inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars Korsbæk Connor; Poulsen, Anne Havemose; Bendtzen, Klaus

    2009-01-01

    -inflammatory cytokines and cytokine receptors in patients with periodontitis and patients with arthritis representing two examples of chronic inflammatory diseases, such as periodontitis and arthritis. To identify possible disease-specific characteristics of subjects with periodontitis relative to subjects with chronic......TNF-RI plasma levels in patients with LAgP and RA. CONCLUSIONS: The study demonstrated only a few changes in the PBMC expression of various cytokine and cytokine inhibitor genes in aggressive periodontitis and chronic arthritis compared to controls. There were a few similarities among disease groups...... inflammation in general, patients with arthritis (juvenile idiopathic arthritis [JIA] and rheumatoid arthritis [RA]) were included. METHODS: The study population consisted of white adults periodontitis (LAgP; n = 18), generalized aggressive periodontitis...

  13. Triterpenoid saponins from Polaskia chichipe Backbg. and their inhibitory or promotional effects on the melanogenesis of B16 melanoma cells.

    Science.gov (United States)

    Fujihara, Koji; Takahashi, Kunio; Koyama, Kiyotaka; Kinoshita, Kaoru

    2017-10-01

    Five new oleanane-type saponins 1-5 together with a known saponin 6 and a steroidal glycoside 7 were isolated from Polaskia chichipe Backbg., and their structures were determined from their 1D and 2D NMR and HRFABMS spectral data. The six isolated saponins 1-6 were tested for their effects on the melanogenesis of B16 melanoma 4A5 cells. Compound 1 exerted an inhibitory effect at 100 μM whereas compound 3 promoted melanogenesis at the same concentration, even though these two compounds contain the same aglycon structure. The dose-dependent activities of compounds 1 and 3 on melanin synthesis were investigated.

  14. Do detour tasks provide accurate assays of inhibitory control?

    Science.gov (United States)

    Whiteside, Mark A.; Laker, Philippa R.; Beardsworth, Christine E.

    2018-01-01

    Transparent Cylinder and Barrier tasks are used to purportedly assess inhibitory control in a variety of animals. However, we suspect that performances on these detour tasks are influenced by non-cognitive traits, which may result in inaccurate assays of inhibitory control. We therefore reared pheasants under standardized conditions and presented each bird with two sets of similar tasks commonly used to measure inhibitory control. We recorded the number of times subjects incorrectly attempted to access a reward through transparent barriers, and their latencies to solve each task. Such measures are commonly used to infer the differential expression of inhibitory control. We found little evidence that their performances were consistent across the two different Putative Inhibitory Control Tasks (PICTs). Improvements in performance across trials showed that pheasants learned the affordances of each specific task. Critically, prior experience of transparent tasks, either Barrier or Cylinder, also improved subsequent inhibitory control performance on a novel task, suggesting that they also learned the general properties of transparent obstacles. Individual measures of persistence, assayed in a third task, were positively related to their frequency of incorrect attempts to solve the transparent inhibitory control tasks. Neophobia, Sex and Body Condition had no influence on individual performance. Contrary to previous studies of primates, pheasants with poor performance on PICTs had a wider dietary breadth assayed using a free-choice task. Our results demonstrate that in systems or taxa where prior experience and differences in development cannot be accounted for, individual differences in performance on commonly used detour-dependent PICTS may reveal more about an individual's prior experience of transparent objects, or their motivation to acquire food, than providing a reliable measure of their inhibitory control. PMID:29593115

  15. Optimization of inhibitory decision rules relative to length and coverage

    KAUST Repository

    Alsolami, Fawaz

    2012-01-01

    The paper is devoted to the study of algorithms for optimization of inhibitory rules relative to the length and coverage. In contrast with usual rules that have on the right-hand side a relation "attribute ≠ value", inhibitory rules have a relation "attribute = value" on the right-hand side. The considered algorithms are based on extensions of dynamic programming. © 2012 Springer-Verlag.

  16. Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders

    Science.gov (United States)

    2016-12-01

    1 AWARD NUMBER: W81XWH-14-1-0433 TITLE: Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders PRINCIPAL INVESTIGATOR: Anis...SUBTITLE 5a. CONTRACT NUMBER Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0433 5c. PROGRAM...chloride co-transporters that control EGABA could be used as a corrective strategy for the synaptic and circuit disruptions demonstrated in the

  17. Voluntary inhibitory motor control over involuntary tic movements.

    Science.gov (United States)

    Ganos, Christos; Rothwell, John; Haggard, Patrick

    2018-03-06

    Inhibitory control is crucial for normal adaptive motor behavior. In hyperkinesias, such as tics, disinhibition within the cortico-striato-thalamo-cortical loops is thought to underlie the presence of involuntary movements. Paradoxically, tics are also subject to voluntary inhibitory control. This puzzling clinical observation questions the traditional definition of tics as purely involuntary motor behaviors. Importantly, it suggests novel insights into tic pathophysiology. In this review, we first define voluntary inhibitory tic control and compare it with other notions of tic control from the literature. We then examine the association between voluntary inhibitory tic control with premonitory urges and review evidence linking voluntary tic inhibition to other forms of executive control of action. We discuss the somatotopic selectivity and the neural correlates of voluntary inhibitory tic control. Finally, we provide a scientific framework with regard to the clinical relevance of the study of voluntary inhibitory tic control within the context of the neurodevelopmental disorder of Tourette syndrome. We identify current knowledge gaps that deserve attention in future research. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  18. Self-reported impulsivity and inhibitory control in problem gamblers.

    Science.gov (United States)

    Lorains, Felicity K; Stout, Julie C; Bradshaw, John L; Dowling, Nicki A; Enticott, Peter G

    2014-01-01

    Impulsivity is considered a core feature of problem gambling; however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports betting) and nonstrategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task, and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and nonstrategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers.

  19. Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

    Directory of Open Access Journals (Sweden)

    Katherine M. Weh

    2016-08-01

    Full Text Available Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.

  20. Plasma cytokine expression in adolescent chronic fatigue syndrome.

    Science.gov (United States)

    Wyller, Vegard Bruun; Sørensen, Øystein; Sulheim, Dag; Fagermoen, Even; Ueland, Thor; Mollnes, Tom Eirik

    2015-05-01

    Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12-18years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and

  1. 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

    DEFF Research Database (Denmark)

    Müller, K; Haahr, P M; Diamant, M

    1992-01-01

    was not caused by impaired production of mRNA. Taken together, the study demonstrates a vitamin D-induced inhibitory effect of LPS-driven monokine production, which is most likely a vitamin D-receptor mediated phenomenon exerted at a post-transcriptional, presecretory level. Impaired monokine production may...... be of importance in 1,25-(OH)2D3-mediated inhibition of lymphocyte functions in vitro.......1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits lymphocyte proliferation and production of antibodies and lymphokines such as interleukin (IL)-2 and interferon gamma. These lymphocyte functions are dependent upon cytokines, including IL-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor alpha...

  2. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2014-01-01

    Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

  3. Differential effects of Radix Paeoniae Rubra (Chishao on cytokine and chemokine expression inducible by mycobacteria

    Directory of Open Access Journals (Sweden)

    Li James

    2011-03-01

    translocation of transcription factor NF-κB1 p50 to the nucleus. Conclusion RPR crude extracts and its fraction RPR-EA-S1 inhibited anti-inflammatory cytokine IL-10 and enhanced pro-inflammatory chemokine IL-8 expression in BCG-activated PBMac. The inhibitory effects of RPR-EA-S1 on IL-10 expression in BCG-activated PBMac may be due to the reduced nuclear translocation of NF-κB1 p50.

  4. CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

    Directory of Open Access Journals (Sweden)

    L. V. Puzyryova

    2016-01-01

    Full Text Available The molecular genetics opens the new horizons in modern medicine, especially now when many diseases are given huge value in a type of their prevalence among various groups of population. Extremely high interleukin genes polymorphism degrees are studied well especially genetic polymorphism of tumor necrosis factor. Patients with HIV infection in the territory of Russia cause now the highest degree of mortality that is the most actual and socially significant problem of healthcare. This problems studying attracts many researchers. Works in respect of genetic immunity to a virus and influence of cytokines production on the disease forecast are especially interesting. One of the HIV replication influencing factors are cytokines, some of which, including the tumor necrosis factor and interleukin-6 can promote replication of HIV, raising an expression of virus regulatory genes. During disease progress in parallel of anti-inflammatory cytokines level increase (causing in this case rather ineffective antibodies level increase there is an T-helpers suppression stimulating a strong cellular component. Cytokine network functioning during HIV infection depends on many reasons which the individual variation in cytokine production caused by a number of genetic features, as well as an existence of opportunistic infection. Cytokines polymorphism determination in HIV infected patients is necessary in clinical practice for disease progression forecast to adverse fast transition to AIDS that it is important to consider in a choice of tactics of the supporting therapy of HIV-positive patients. Considering insufficient efficiency of modern methods of treatment, restoration and modulation of cytokines balance will increase anti-virus activity of immune system, influencing the factors blocking replication of a HIV.

  5. Organic synthesis

    International Nuclear Information System (INIS)

    Lallemand, J.Y.; Fetizon, M.

    1988-01-01

    The 1988 progress report of the Organic Synthesis Chemistry laboratory (Polytechnic School, France), is presented. The laboratory activities are centered on the chemistry of natural products, which have a biological activity and on the development of new reactions, useful in the organic synthesis. The research works involve the following domains: the natural products chemistry which are applied in pharmacology, the plants and insects chemistry, the organic synthesis, the radical chemistry new reactions and the bio-organic physicochemistry. The published papers, the congress communications and the thesis are listed [fr

  6. Erythropoietin level in acute plasmodium falicparum malaria in relation to prainflammatory cytokines and antimalarial drugs

    International Nuclear Information System (INIS)

    Mohamed, Adil Ballal

    2000-03-01

    Malaria is a major health problem in tropical areas. Anaemia is a serious complication of this parasitic infection and an important issue in malaria research. Along this line the haematological parameters, EPO level and proinflammatory cytokines (TNF-∝ and IFN-γ, IL-6 and IL-I β) for 40 P. falciparum malaria patients and 37 control subjects were measured before and three and thirty days after commencing the chloroquine treatment. The mean ± SEM haemoglobin concentration of malaria patient in day 0, was found to be significantly lower (130±1.33g/l than of control subjects (158±1.89g/l), anaemia as haemoglobin of less than (119 g/l) was reported in only one of our patients. On the other hand no significant difference was observed in EPO level in malaria patients were significantly increased thirty days after chloroquine intake. Also we reported a highly significant increase in TNFα and in the sera of malaria patients before treatment, this initial level decreased following chloroquine treatment on day thirty. This finding was on line with the other studies which suggested the therapeutic effects of choloroquine in inflammatory disease is due to its inhibitory effect o TNF secretion. With respect to concentration of IFN-α the initial increase before treatment, decrease following treatment. The concentration of the monokine IL-I β-and IL-6 showed much smaller changes in malaria patients before and following chloroquine treatment, in comparison to non-infective controls. The study on tissue culture showed that choloroquine and quinine decrease EPO production by viability and RT-PCR analysis for housekeeping gene β-action. In conclusion prolonged elevation in TNF-α level which reduces EPO production, might contribute to the anaemia in some malaria patients. Chloroquine exerted an inhibitory effect on EPO production in vivo as well as in vitro, nevertheless it has a beneficial effect as anti-disease therapy due to its potent inhibitory effect on TNF

  7. Decorrelation of Neural-Network Activity by Inhibitory Feedback

    Science.gov (United States)

    Einevoll, Gaute T.; Diesmann, Markus

    2012-01-01

    Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

  8. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis

    International Nuclear Information System (INIS)

    Rubin, Philip; Johnston, Carl J.; Williams, Jacqueline P.; McDonald, Sandra; Finkelstein, Jacob N.

    1995-01-01

    Purpose: Radiation-induced pulmonary reactions have classically been viewed as distinct phases--acute pneumonitis and, later, fibrosis--occurring at different times after irradiation and attributed to different target cell populations. We prefer to view these events as a continuum, with no clear distinction between the temporal sequence of the different pulmonary reactions; the progression is the result of an early activation of an inflammatory reaction, leading to the expression and maintenance of a cytokine cascade. In the current study, we have examined the temporal and spatial expression of cytokine and extracellular matrix messenger ribonucleic acid (mRNA) abundance in fibrosis-sensitive mice after thoracic irradiation. Methods and Materials: Radiation fibrosis-prone ((C57BL(6))) mice received thoracic irradiation of 5 and 12.5 Gy. At Day 1, and 1, 2, 8, 16 and 24 weeks after treatment, animals were killed and lung tissue processed for light microscopy and isolation of RNA. Expression of cytokine and extracellular matrix mRNA abundance was evaluated by slot-blot analysis and cellular localization by in situ hybridization and immunochemistry. Results: One of the cytokines responsible for the inflammatory phase (IL-1α) is elevated at 2 weeks, returns to normal baseline values, then increases at 8 weeks, remaining elevated until 26 weeks when lung fibrosis appears. Transforming growth factor-beta (TGFβ), a proliferative cytokine, is elevated at 2 weeks, persists until 8 weeks, and then returns to baseline values. In parallel with the cytokine cascade, the fibrogenic markers for CI/CIII/IV (collagen genes) correlate by showing a similar early and then later elevation of activity. For instance, the collagen gene expression of CI/CIII is a biphasic response with an initial increase at 1-2 weeks that remits at 8 weeks, remains inactive from 8 to 16 weeks, and then becomes elevated at 6 months when collagen deposition is recognized histopathologically. Conclusion

  9. Twenty Years of Research on Cytokine-Induced Sickness Behavior*

    Science.gov (United States)

    Dantzer, Robert; Kelley, Keith W.

    2007-01-01

    Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-α, IL-1 and IL-2, which occurred around the time that the first issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinflammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was defined as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism's priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve. The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimers' disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the

  10. Leukemia inhibitory factor tips the immune balance towards regulatory T cells in multiple sclerosis.

    Science.gov (United States)

    Janssens, Kris; Van den Haute, Chris; Baekelandt, Veerle; Lucas, Sophie; van Horssen, Jack; Somers, Veerle; Van Wijmeersch, Bart; Stinissen, Piet; Hendriks, Jerome J A; Slaets, Helena; Hellings, Niels

    2015-03-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), for which current treatments are unable to prevent disease progression. Based on its neuroprotective and neuroregenerating properties, leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is proposed as a novel candidate for MS therapy. However, its effect on the autoimmune response remains unclear. In this study, we determined how LIF modulates T cell responses that play a crucial role in the pathogenesis of MS. We demonstrate that expression of the LIF receptor was strongly increased on immune cells of MS patients. LIF treatment potently boosted the number of regulatory T cells (Tregs) in CD4(+) T cells isolated from healthy controls and MS patients with low serum levels of IL-6. Moreover, IL-6 signaling was reduced in the donors that responded to LIF treatment in vitro. Our data together with previous findings revealing that IL-6 inhibits Treg development, suggest an opposing function of LIF and IL-6. In a preclinical animal model of MS we shifted the LIF/IL-6 balance in favor of LIF by CNS-targeted overexpression. This increased the number of Tregs in the CNS during active autoimmune responses and reduced disease symptoms. In conclusion, our data show that LIF downregulates the autoimmune response by enhancing Treg numbers, providing further impetus for the use of LIF as a novel treatment for MS and other autoimmune diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Macrophage Migration Inhibitory Factor-Induced Autophagy Contributes to Thrombin-Triggered Endothelial Hyperpermeability in Sepsis.

    Science.gov (United States)

    Chao, Chiao-Hsuan; Chen, Hong-Ru; Chuang, Yung-Chun; Yeh, Trai-Ming

    2018-07-01

    Vascular leakage contributes to the high morbidity and mortality associated with sepsis. Exposure of the endothelium to inflammatory mediators, such as thrombin and cytokines, during sepsis leads to hyperpermeability. We recently observed that autophagy, a cellular process for protein turnover, is involved in macrophage migration inhibitory factor (MIF)-induced endothelial hyperpermeability. Even though it is known that thrombin induces endothelial cells to secrete MIF and to increase vascular permeability, the possible role of autophagy in this process is unknown. In this study, we proposed and tested the hypothesis that MIF-induced autophagy plays an important role in thrombin-induced endothelial hyperpermeability. We evaluated the effects of thrombin on endothelial permeability, autophagy induction, and MIF secretion in vitro using the human microvascular endothelial cell line-1 and human umbilical vein endothelial cells. Several mechanisms/read outs of endothelial permeability and autophagy formation were examined. We observed that blocking autophagy attenuated thrombin-induced endothelial hyperpermeability. Furthermore, thrombin-induced MIF secretion was involved in this process because MIF inhibition reduced thrombin-induced autophagy and hyperpermeability. Finally, we showed that blocking MIF or autophagy effectively alleviated vascular leakage and mortality in endotoxemic mice. Thus, MIF-induced autophagy may represent a common mechanism causing vascular leakage in sepsis.

  12. Macrophage Migration Inhibitory Factor Polymorphism Is Associated with Susceptibility to Inflammatory Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Kangting Ji

    2015-01-01

    Full Text Available Background. Macrophage migration inhibitory factor (MIF is a proinflammatory cytokine. This study explored the association of 173G/C polymorphism of the MIF gene with coronary heart disease (CHD. Methods. Sequencing was carried out after polymerase chain reaction with DNA specimens from 186 volunteers without CHD and 70 patients with CHD. Plasma MIF levels on admission were measured by ELISA. Patients were classified into either stable angina pectoris (SAP or unstable angina pectoris (UAP. Genotype distribution between cases and controls and the association of patients’ genotypes with MIF level and plaque stability were statistically evaluated (ethical approval number: 2012-01. Results. The frequency of the C genotype was higher in CHD patients than in the control (P=0.014. The frequency of the 173*CC genotype was higher in CHD patients than in the control (P=0.005. The plasma MIF level was higher in MIF173*C carriers than in MIF173*G carriers (P=0.033. CHD patients had higher plasma MIF levels than the control (P=0.000. Patients with UAP had higher plasma MIF levels than patients with SAP (P=0.014. Conclusions. These data suggest that MIF −173G/C polymorphism may be related to the development of CHD in a Chinese population. Plasma MIF level is a predictor of plaque stability. This trial is registered with NCT01750502 .

  13. Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics.

    Science.gov (United States)

    Uzunova, Genoveva; Pallanti, Stefano; Hollander, Eric

    2016-04-01

    Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a "minicolumnopathy". E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.

  14. Evidence for a role of macrophage migration inhibitory factor in vascular disease.

    Science.gov (United States)

    Chen, Zhiping; Sakuma, Masashi; Zago, Alexandre C; Zhang, Xiaobin; Shi, Can; Leng, Lin; Mizue, Yuka; Bucala, Richard; Simon, Daniel

    2004-04-01

    Inflammation plays an essential role in atherosclerosis and restenosis. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is widely expressed in vascular cells. However, there is no in vivo evidence that MIF participates directly in vascular injury and repair. Therefore, we investigated the effect of MIF blockade on the response to experimental angioplasty in atherosclerosis-susceptible mice. Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDL receptor-deficient mice treated with a neutralizing anti-MIF or isotype control monoclonal antibody. After 7 days and 28 days, intimal and medial sizes were measured and intima/media area ratio (I/M) was calculated. Intimal thickening and I/M were reduced significantly by anti-MIF compared with control antibody. Vascular injury was accompanied by progressive vessel enlargement or "positive remodeling" that was comparable in both treatment groups. MIF blockade was associated with reduced inflammation and cellular proliferation and increased apoptosis after injury. Neutralizing MIF bioactivity after experimental angioplasty in atherosclerosis-susceptible mice reduces vascular inflammation, cellular proliferation, and neointimal thickening. Although the molecular mechanisms responsible for these effects are not yet established, these data prompt further research directed at understanding the role of MIF in vascular disease and suggest novel therapeutic interventions for preventing atherosclerosis and restenosis.

  15. Th1/Th2 cytokine expression in diabetic retinopathy.

    Science.gov (United States)

    Cao, Y L; Zhang, F Q; Hao, F Q

    2016-07-15

    Diabetic retinopathy (DR), an important complication of diabetes mellitus (DM), is not well understood. T helper cell balance (Th1/Th2) is involved in various autoimmune diseases; however, its role in DR is not understood. This study explores changes in Th1 and Th2 cytokine expression during DR. Blood samples were collected from 25 healthy volunteers (normal control group), 35 patients with type 2 DM (T2DM group) without DR, and 30 cases of T2DM patients with DR (DR group). Real-time PCR was used to measure mRNA expression of IL-2 and TNF-α, secreted from Th1 cells, and of IL-4 and IL-10, secreted from Th2 cells. We used ELISA to detect cytokine expression in serum to analyze the correlation between Th1 and Th2 cytokines. IL-2 and TNF-αmRNA and protein expression levels in the T2DM and DR groups were significantly higher than in the normal control group (P 0.05). IL-2 and TNF-αwere negatively correlated with IL-4 and IL-10 in the DR group, respectively. We found that Th1 cytokine secretion was higher and Th2 cytokines secretion was lower during DR, leading to a Th1/ Th2 imbalance, suggesting that Th1/Th2 imbalance is a side effect for DR occurrence and development.

  16. Serum Cytokine Profiles in Children with Crohn’s Disease

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    Ekaterina Vasilyeva

    2016-01-01

    Full Text Available Crohn’s disease (CD is a chronic inflammatory bowel disease that can be diagnosed at any age. There are two major patient groups based on diagnosis of this disease, before or after the age of 20 (juvenile/adolescent or adult, with disease progression in adults usually milder than in juvenile CD patients. Immune mechanisms have been suggested to play an important role in CD pathogenesis, with cytokines governing the development of the immune response. Upregulation of inflammatory cytokines in serum of juvenile and adult CD patients has been documented; still little is known about age-dependent differences in serum cytokine profiles of CD patients. We applied multiplex technology to analyze serum levels of 12 cytokines in juveniles and adults. We show that during the acute stage of the disease all CD patients have high serum levels of CXCL10, which remains upregulated during remission. Increased serum levels of TNF-α and IL-6 during the acute stage was characteristic of juvenile CD patients, whereas adult CD patients had upregulated levels of GM-CSF and IFN-γ. Taken together, these results demonstrate age-dependent differences in cytokine profiles, which may affect the pathogenesis of CD in patients at different ages of disease onset.

  17. Cytokine changes in tears and relationship to contact lens discomfort.

    Science.gov (United States)

    Willcox, Mark D P; Zhao, Zhenjun; Naduvilath, Thomas; Lazon de la Jara, Percy

    2015-01-01

    To determine the reproducibility of a multiplex bead assay for measuring cytokines in tears and correlations between ocular discomfort with or without contact lens wear and the concentration of cytokines in tears. Ninety participants (divided into two groups) were enrolled in this prospective study. They were asked to rate their ocular comfort and collect their tears in the morning and just before sleep for 10 days with or without contact lenses. The participants collected their tears using a glass microcapillary tube for both stages. Galyfilcon A lenses were worn on a daily disposable basis during the contact lens stage, and comfort scores and tears were collected before lens insertion and prior to lens removal at the end of the day. Tears were analyzed for cytokine concentrations using a 27-plex multibead assay. Correlations were sought between cytokine concentrations and comfort. There was a significant (p-0.5 Log pg/ml, p-0.2 Log pg/ml, ptears was correlated to ocular comfort, but this was not changed by contact lens wear. Ocular comfort during the day is magnified by contact lens wear. However, the increase in the change in comfort during lens wear was not associated with changes in 15 cytokines in the tear film.

  18. Instruction of hematopoietic lineage choice by cytokine signaling

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    Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

    2014-12-10

    Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

  19. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    Science.gov (United States)

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  20. Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

    Science.gov (United States)

    Foster, Meika; Samman, Samir

    2012-01-01

    In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

  1. Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

    Science.gov (United States)

    Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

    2017-11-01

    In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

  2. Cytokine-Like Protein 1(Cytl1: A Potential Molecular Mediator in Embryo Implantation.

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    Zhichao Ai

    Full Text Available Cytokine-like protein 1 (Cytl1, originally described as a protein expressed in CD34+ cells, was recently identified as a functional secreted protein involved in chondrogenesis and cartilage development. However, our knowledge of Cytl1 is still limited. Here, we determined the Cytl1 expression pattern regulated by ovarian hormones at both the mRNA and protein levels. We found that the endometrial expression of Cytl1 in mice was low before or on the first day of gestation, significantly increased during embryo implantation, and then decreased at the end of implantation. We investigated the effects of Cytl1 on endometrial cell proliferation, and the effects on the secretion of leukemia inhibitory factor (LIF and heparin-binding epidermal growth factor (HB-EGF. We also explored the effect of Cytl1 on endometrial adhesion properties in cell-cell adhesion assays. Our findings demonstrated that Cytl1 is an ovarian hormone-dependent protein expressed in the endometrium that enhances the proliferation of HEC-1-A and RL95-2 cells, stimulates endometrial secretion of LIF and HB-EGF, and enhances the adhesion of HEC-1-A and RL95-2 cells to JAR spheroids. This study suggests that Cytl1 plays an active role in the regulation of embryo implantation.

  3. Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

    Science.gov (United States)

    Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

    2012-01-01

    Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

  4. Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2011-01-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

  5. Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

    Science.gov (United States)

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2012-03-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele.

  6. Effect of Macrophage Migration Inhibitory Factor (MIF) in Human Placental Explants Infected with Toxoplasma gondii Depends on Gestational Age

    Science.gov (United States)

    de Oliveira Gomes, Angelica; de Oliveira Silva, Deise Aparecida; Silva, Neide Maria; de Freitas Barbosa, Bellisa; Franco, Priscila Silva; Angeloni, Mariana Bodini; Fermino, Marise Lopes; Roque-Barreira, Maria Cristina; Bechi, Nicoletta; Paulesu, Luana Ricci; dos Santos, Maria Célia; Mineo, José Roberto; Ferro, Eloisa Amália Vieira

    2011-01-01

    Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-β1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age. PMID:21641401

  7. Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus.

    Science.gov (United States)

    Zhang, Xiao-Xia; Wu, Qiao-Feng; Yan, Yun-Liang; Zhang, Feng-Ling

    2018-02-01

    The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues. We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment. This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

  8. 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.

  9. COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain.

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    Rawan Abdulhameed Edan

    Full Text Available Microglia activation results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the central nervous system (CNS if not controlled. Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In the present study we found that administration of chemically modified tetracycline-3 (COL-3, inhibits lipopolysaccharide (LPS-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice. COL-3 has been described to have no antibacterial activity. We observed that COL-3 had no activity against a Gram-negative bacteria, Escherichia coli; however surprisingly, COL-3 had antibacterial activity against a Gram-positive bacteria Staphylococcus aureus, with a minimum inhibitory concentration of 1 mg/ml. Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

  10. Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

    Science.gov (United States)

    Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

    2018-05-04

    Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

  11. Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines.

    Science.gov (United States)

    Yi, Qiu-Yue; Li, Hong-Bao; Qi, Jie; Yu, Xiao-Jing; Huo, Chan-Juan; Li, Xiang; Bai, Juan; Gao, Hong-Li; Kou, Bo; Liu, Kai-Li; Zhang, Dong-Dong; Chen, Wen-Sheng; Cui, Wei; Zhu, Guo-Qing; Shi, Xiao-Lian; Kang, Yu-Ming

    2016-11-16

    Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-κB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) rats and SHR received bilateral PVN infusion of EGCG (20μg/h) or vehicle via osmotic minipumps for 4 weeks. SHR showed higher mean arterial pressure, plasma proinflammatory cytokines and circulating norepinephrine (NE) levels compared with WKY rats. SHR also had higher PVN levels of the subunit of NAD(P)H oxidase (gp91 phox ), ROS, tyrosine hydroxylase, and PICs; increased NF-κB activity; and lower PVN levels of interleukin-10 (IL-10) and 67kDa isoform of glutamate decarboxylase (GAD67) than WKY rats. PVN infusion of EGCG attenuated all these changes in SHR. These findings suggest that SHR have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN. Chronic inhibition of ROS in the PVN restores the balance of neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive response and sympathetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Inhibitory receptor expression depends more dominantly on differentiation and activation than exhaustion of human CD8 T cells

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    Amandine eLegat

    2013-12-01

    Full Text Available Under conditions of chronic antigen stimulation, such as persistent viral infection and cancer, CD8 T cells may diminish effector function, which has been termed exhaustion. Expression of inhibitory Receptors (iRs is often regarded as a hallmark of exhaustion. Here we studied the expression of eight different iRs by CD8 T cells of healthy humans, including CTLA-4, PD1, TIM3, LAG3, 2B4, BTLA, CD160 and KLRG-1. We show that many iRs are expressed upon activation, and with progressive differentiation to effector cells, even in absence of long-term (chronic antigenic stimulation. In particular, we evaluated the direct relationship between iR expression and functionality in CD8 T cells by using anti-CD3 and anti-CD28 stimulation to stimulate all cells and differentiation subsets. We observed a striking upregulation of certain iRs following the cytokine production wave, in agreement with the notion that iRs function as a negative feedback mechanism. Intriguingly, we found no major impairment of cytokine production in cells positive for a broad array of iRs, as previously shown for PD1 in healthy donors. Rather, the expression of the various iRs strongly correlated with T cell differentiation or activation states, or both. Furthermore, we analyzed CD8 T cells from lymph nodes (LNs of melanoma patients. Interestingly, we found altered iR expression and lower cytokine production by T cells from metastatic LNs, but also from non-metastatic LNs, likely due to mechanisms which are not related to exhaustion. Together, our data shows that expression of iRs per se does not mark dysfunctional cells, but is rather tightly linked to activation and differentiation. This study highlights the importance of considering the status of activation and differentiation for the study and the clinical monitoring of CD8 T cells.

  13. Somatostatin-expressing inhibitory interneurons in cortical circuits

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    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  14. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    Directory of Open Access Journals (Sweden)

    Shohei Sakuda

    2014-03-01

    Full Text Available Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control.

  15. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    Science.gov (United States)

    Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

    2014-01-01

    Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

  16. Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection

    DEFF Research Database (Denmark)

    Rønn, S G; Börjesson, A; Bruun, C

    2008-01-01

    The pro-inflammatory cytokines IL-1 and IFNgamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS...

  17. Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

    Science.gov (United States)

    Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

    2013-03-15

    Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

  18. Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes.

    Science.gov (United States)

    Stinson, Lisa F; Ireland, Demelza J; Kemp, Matthew W; Payne, Matthew S; Stock, Sarah J; Newnham, John P; Keelan, Jeffrey A

    2014-03-01

    Intrauterine infection and inflammation are responsible for the majority of early (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3-20  h). In human membranes, the IKKβ inhibitor TPCA-1 (7  μM) and p38 MAPK inhibitor SB239063 (20  μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10  mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10  μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.

  19. Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages.

    Science.gov (United States)

    Budai, Marietta M; Varga, Aliz; Milesz, Sándor; Tőzsér, József; Benkő, Szilvia

    2013-12-01

    Aloe vera has been used in traditional herbal medicine as an immunomodulatory agent inducing anti-inflammatory effects. However, its role on the IL-1β inflammatory cytokine production has not been studied. IL-1β production is strictly regulated both at transcriptional and posttranslational levels through the activity of Nlrp3 inflammasome. In this study we aimed to determine the effect of Aloe vera on the molecular mechanisms of Nlrp3 inflammasome-mediated IL-1β production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Our results show that Aloe vera significantly reduced IL-8, TNFα, IL-6 and IL-1β cytokine production in a dose dependent manner. The inhibitory effect was substantially more pronounced in the primary cells. We found that Aloe vera inhibited the expression of pro-IL-1β, Nlrp3, caspase-1 as well as that of the P2X7 receptor in the LPS-induced primary macrophages. Furthermore, LPS-induced activation of signaling pathways like NF-κB, p38, JNK and ERK were inhibited by Aloe vera in these cells. Altogether, we show for the first time that Aloe vera-mediated strong reduction of IL-1β appears to be the consequence of the reduced expression of both pro-IL-1β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, we show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1β cytokine secretion. These results may provide a new therapeutic approach to regulate inflammasome-mediated responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    International Nuclear Information System (INIS)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L.

    2015-01-01

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS

  1. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

    2015-01-20

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

  2. Serum cytokine levels in Kleine-Levin syndrome

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Rico, Thomas; Lin, Ling

    2015-01-01

    in USA, France, and Taiwan in a clinical setting. Processing of the samples was performed at the Stanford Center for Sleep Sciences and Medicine. RESULTS: We did not observe any changes in serum cytokine levels during KLS episodes compared to between episodes. In a small cohort of asymptomatic KLS...... patients and age- and gender matched healthy controls (n = 8/group) whose blood samples were all collected and processed at the same day; asymptomatic KLS patients had significantly higher levels of serum sVCAM1 cytokine compared to healthy controls. CONCLUSION: These data suggest that KLS episodes...... unknown. The objective of this study was to determine serum cytokine levels in patients with KLS during and between episodes. PATIENTS/METHODS: Fifty-two typical KLS patients were included in the study of whom 17 patients donated blood samples both during and between episodes. Blood samples were collected...

  3. Symposium overview: alterations in cytokine receptors by xenobiotics.

    Science.gov (United States)

    Cohen, M D; Schook, L B; Oppenheim, J J; Freed, B M; Rodgers, K E

    1999-04-01

    A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

  4. CYTOKINE PROFILE FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    E. Р. Kalinina

    2012-01-01

    Full Text Available Abstract. We studied cytokine profile in blood and exhaled breath condensate (EBC in patients with chronic obstructive pulmonary disease (COPD being in remission state. It is shown that pro- and anti-inflammatory cytokine contents depended on the disease severity, both in whole blood and EBC of the COPD patients. We have revealed an increase in TNFα, s-TNFα RI, TGF-β1 and bFGF in EBC of patients with COPD manifestations, thus being indicative for progression of metabolic changes in lung tissue, and advanced stage of respiratory functional disturbances. Cytokine profile abnormalities in COPD patients resulting, in part, from systemic and local disorders of cellular immunity, represent a major pathogenetic mechanism determining the disease progression.

  5. Proinflammatory cytokine levels in patients with conversion disorder.

    Science.gov (United States)

    Tiyekli, Utkan; Calıyurt, Okan; Tiyekli, Nimet Dilek

    2013-06-01

    It was aimed to evaluate the relationship between proinflammatory cytokine levels and conversion disorder both commonly known as stress regulated. Baseline proinflammatory cytokine levels-[Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)]-were evaluated with enzyme-linked immunosorbent assay in 35 conversion disorder patients and 30 healthy controls. Possible changes in proinflammatory cytokine levels were evaluated again, after their acute phase in conversion disorder patients. Statistically significant decreased serum TNF-α levels were obtained in acute phase of conversion disorder. Those levels increased after acute conversion phase. There were no statistically significant difference observed between groups in serum IL-1β and (IL-6) levels. Stress associated with conversion disorder may suppress immune function in acute conversion phase and may have diagnostic and therapeutic value.

  6. Dysregulation of suppressor of cytokine signaling 3 in keratinocytes causes skin inflammation mediated by interleukin-20 receptor-related cytokines.

    Directory of Open Access Journals (Sweden)

    Ayako Uto-Konomi

    Full Text Available Homeostatic regulation of epidermal keratinocytes is controlled by the local cytokine milieu. However, a role for suppressor of cytokine signaling (SOCS, a negative feedback regulator of cytokine networks, in skin homeostasis remains unclear. Keratinocyte specific deletion of Socs3 (Socs3 cKO caused severe skin inflammation with hyper-production of IgE, epidermal hyperplasia, and S100A8/9 expression, although Socs1 deletion caused no inflammation. The inflamed skin showed constitutive STAT3 activation and up-regulation of IL-6 and IL-20 receptor (IL-20R related cytokines, IL-19, IL-20 and IL-24. Disease development was rescued by deletion of the Il6 gene, but not by the deletion of Il23, Il4r, or Rag1 genes. The expression of IL-6 in Socs3 cKO keratinocytes increased expression of IL-20R-related cytokines that further facilitated STAT3 hyperactivation, epidermal hyperplasia and neutrophilia. These results demonstrate that skin homeostasis is strictly regulated by the IL-6-STAT3-SOCS3 axis. Moreover, the SOCS3-mediated negative feedback loop in keratinocytes has a critical mechanistic role in the prevention of skin inflammation caused by hyperactivation of STAT3.

  7. Cytokine and chemokine levels in tears from healthy subjects.

    Science.gov (United States)

    Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

    2010-11-01

    There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

  8. Tributyltin exposure alters cytokine levels in mouse serum.

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  9. Tributyltin Exposure Alters Cytokine Levels in Mouse Serum

    Science.gov (United States)

    Lawrence, Shanieek; Pellom, Samuel T.; Shanker, Anil; Whalen, Margaret M.

    2016-01-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines. PMID:27602597

  10. The Role of Cytokines in the Pathophysiology of Suicidal Behavior

    Science.gov (United States)

    Ganança, Licínia; Oquendo, Maria A.; Tyrka, Audrey R.; Cisneros-Trujillo, Sebastian; Mann, J. John; Sublette, M. Elizabeth

    2016-01-01

    Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk. PMID:26546783

  11. Low dose radiation enhancing inhibitory effect of tumor-associated antigen peptide extract on H-22 hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zuyue, Sun; Jingyi, Fu; Yong, Zhao [Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Inst. of Zoology, Chinese Academy of Sciences, Beijing (China); Jianxiang, Liu; Zhibo, Fu; Xiuyi, Li; Shuzheng, Liu; Shouliang, Gong

    2005-06-15

    Objective: To determine whether there is synergically inhibitory effect of low dose radiation (LDR) and tumor-associated antigen peptides (TAP) on tumor growth in vivo, which may provide experimental basis for potential clinical co-application of these two approaches to treat cancers. Methods: TAP extract (MW {<=}3x10{sup 6}) from tumor cell membrane was prepared with mild acid elution method , as reported. The mice were whole-bodily irradiated with 75 mGy X-rays 12 h before immunization with TAP extract. After immunization , the levels of CD3, CD69, TCR{alpha}{beta} cells and T cell subsets in the spleen were detected with FACS. The tumor growth rate was estimated, and the responses to Con A, the cytokine productions and CTL activities of splenocytes were also analyzed 7 d after immunization with TAP. Results: The present experimental results showed that the TAP extract significantly reduced the incidence of the transplanted tumor, delayed the average appearing time and decreased the growth speed of the tumor. The response of splenocytes from mice immunized with TAP extract to Con A increased significantly compared with that in the control group. Irradiation with 75 mGy X-rays 12 h before immunization further enhanced the inhibitory effect of TAP extract on tumor growth, and increased the percentage of CD8{sup +} splenocytes. Conclusion: These results suggest that whole-body irradiation with LDR exerts a synergic inhibitory effect with TAP on tumor growth in vivo, in which enhanced cellular immune responses may be involved. (authors)

  12. The Role of Cytokines and Chemokines in Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Sandra L. Bixler

    2015-10-01

    Full Text Available Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology.

  13. The Role of Cytokines and Chemokines in Filovirus Infection.

    Science.gov (United States)

    Bixler, Sandra L; Goff, Arthur J

    2015-10-23

    Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology.

  14. NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

    Science.gov (United States)

    Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

    2000-01-01

    A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

  15. Modifying yeast tolerance to inhibitory conditions of ethanol production processes

    Directory of Open Access Journals (Sweden)

    Luis eCaspeta

    2015-11-01

    Full Text Available Saccharomyces cerevisiae strains having a broad range of substrate utilization, rapid substrate consumption and conversion to ethanol, as well as good tolerance to inhibitory conditions are ideal for cost-competitive ethanol production from lignocellulose. A major drawback to directly design S. cerevisiae tolerance to inhibitory conditions of lignocellulosic ethanol production processes is the lack of knowledge about basic aspects of its cellular signaling network in response to stress. Here we highlight the inhibitory conditions found in ethanol production processes, the targeted cellular functions, the key contributions of integrated –omics analysis to reveal cellular stress responses according to these inhibitors, and current status on design-based engineering of tolerant and efficient S. cerevisiae strains for ethanol production from lignocellulose.

  16. Modifying Yeast Tolerance to Inhibitory Conditions of Ethanol Production Processes

    DEFF Research Database (Denmark)

    Caspeta, Luis; Castillo, Tania; Nielsen, Jens

    2015-01-01

    Saccharomyces cerevisiae strains having a broad range of substrate utilization, rapid substrate consumption, and conversion to ethanol, as well as good tolerance to inhibitory conditions are ideal for cost-competitive ethanol production from lignocellulose. A major drawback to directly design S....... cerevisiae tolerance to inhibitory conditions of lignocellulosic ethanol production processes is the lack of knowledge about basic aspects of its cellular signaling network in response to stress. Here, we highlight the inhibitory conditions found in ethanol production processes, the targeted cellular...... functions, the key contributions of integrated -omics analysis to reveal cellular stress responses according to these inhibitors, and current status on design-based engineering of tolerant and efficient S. cerevisiae strains for ethanol production from lignocellulose....

  17. Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen-N-acetyl cysteine-thioester (F-NAC) and fenbufen...... and fenbufen show any protective effect on fenbufen mediated inhibition of oxidative phosphorylation. Inclusion of NADPH in mitochondrial preparations with fenbufen did not modulate the inhibitory effects, suggesting no role of CYP mediated oxidative metabolites on the ATP synthesis in isolated mitochondria...

  18. Inhibitory Effect of Corn Silk on Skin Pigmentation

    OpenAIRE

    Sang Yoon Choi; Yeonmi Lee; Sung Soo Kim; Hyun Min Ju; Ji Hwoon Baek; Chul-Soo Park; Dong-Hyuk Lee

    2014-01-01

    In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin prod...

  19. New polyacetylenes glycoside from Eclipta prostrate with DGAT inhibitory activity.

    Science.gov (United States)

    Meng, Xiao; Li, Ban-Ban; Lin, Xin; Jiang, Yi-Yu; Zhang, Le; Li, Hao-Ze; Cui, Long

    2018-06-08

    One new polyacetylene glycoside eprostrata Ⅰ (1), together with seven known compounds (2-8), were isolated from Eclipta prostrata. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated inhibitory activity on DGAT in an in vitro assay. Compounds 1-8 were found to exhibit inhibitory activity of DGAT1 with IC 50 values ranging from 74.4 ± 1.3 to 101.1 ± 1.1 μM.

  20. Optimization of Approximate Inhibitory Rules Relative to Number of Misclassifications

    KAUST Repository

    Alsolami, Fawaz

    2013-10-04

    In this work, we consider so-called nonredundant inhibitory rules, containing an expression “attribute:F value” on the right- hand side, for which the number of misclassifications is at most a threshold γ. We study a dynamic programming approach for description of the considered set of rules. This approach allows also the optimization of nonredundant inhibitory rules relative to the length and coverage. The aim of this paper is to investigate an additional possibility of optimization relative to the number of misclassifications. The results of experiments with decision tables from the UCI Machine Learning Repository show this additional optimization achieves a fewer misclassifications. Thus, the proposed optimization procedure is promising.

  1. Myostatin inhibitory region of fish (Paralichthys olivaceus) myostatin-1 propeptide.

    Science.gov (United States)

    Lee, Sang Beum; Kim, Jeong Hwan; Jin, Deuk-Hee; Jin, Hyung-Joo; Kim, Yong Soo

    2016-01-01

    Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth, and its activity is suppressed by MSTN propeptide (MSTNpro), the N-terminal part of MSTN precursor cleaved during post-translational MSTN processing. The current study examined which region of flatfish (Paralichthys olivaceus) MSTN-1 propeptide (MSTN1pro) is critical for MSTN inhibition. Six different truncated forms of MSTN1pro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in Escherichia coli, and partially purified by an affinity chromatography for MSTN-inhibitory activity examination. Peptides covering different regions of flatfish MSTN1pro were also synthesized for MSTN-inhibitory activity examination. A MBP-fused MSTN1pro region consisting of residues 45-100 had the same MSTN-inhibitory potency as the full sequence flatfish MSTN1pro (residues 23-265), indicating that the region of flatfish MSTN1pro consisting of residues 45-100 is sufficient to maintain the full MSTN-inhibitory capacity. A MBP-fused MSTN1pro region consisting of residues 45-80 (Pro45-80) also showed MSTN-inhibitory activity with a lower potency, and the Pro45-80 demonstrated its MSTN binding capacity in a pull-down assay, indicating that the MSTN-inhibitory capacity of Pro45-80 is due to its binding to MSTN. Flatfish MSTN1pro synthetic peptides covering residues 45-65, 45-70, and 45-80 demonstrated MSTN-inhibitory activities, but not the synthetic peptide covering residues 45-54, indicating that residues 45-65 of flatfish MSTN1pro are essential for MSTN inhibition. In conclusion, current study show that like the mammalian MSTNpro, the MSTN-inhibitory region of flatfish MSTN1pro resides near its N-terminus, and imply that smaller sizes of MSTNpro can be effectively used in various applications designed for MSTN inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.

    Science.gov (United States)

    Popov, Tzvetan; Westner, Britta U; Silton, Rebecca L; Sass, Sarah M; Spielberg, Jeffrey M; Rockstroh, Brigitte; Heller, Wendy; Miller, Gregory A

    2018-05-02

    Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color-word Stroop task. Time-frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation. SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to

  3. Characterization of a translation inhibitory protein from Luffa aegyptiaca.

    Science.gov (United States)

    Ramakrishnan, S; Enghlid, J J; Bryant, H L; Xu, F J

    1989-04-28

    A protein with a molecular weight of about 30,000 was purified from the seeds of Luffa aegyptiaca. This protein inhibited cell free translation at pM concentrations. In spite of functional similarity to other ribosomal inhibitory proteins, the NH2-terminal analysis did not show any significant homology. Competitive inhibition studies indicate no immunological crossreactivity between the inhibitory protein from Luffa aegyptiaca, pokeweed antiviral protein (PAP) and recombinant ricin A chain. Chemical linkage of the protein to a monoclonal antibody reactive to transferrin receptor resulted in a highly cytotoxic conjugate.

  4. NAMPT-mediated salvage synthesis of NAD+ controls morphofunctional changes of macrophages.

    Directory of Open Access Journals (Sweden)

    Gerda Venter

    Full Text Available Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H (i.e. NAD+ and NADH and NADP(H (i.e. NADP+ and NADPH play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT, found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+'s cytosolic role in the regulation of morphofunctional characteristics of macrophages.

  5. NAMPT-Mediated Salvage Synthesis of NAD+ Controls Morphofunctional Changes of Macrophages

    Science.gov (United States)

    Venter, Gerda; Oerlemans, Frank T. J. J.; Willemse, Marieke; Wijers, Mietske; Fransen, Jack A. M.; Wieringa, Bé

    2014-01-01

    Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H) (i.e. NAD+ and NADH) and NADP(H) (i.e. NADP+ and NADPH) play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT), found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+’s cytosolic role in the regulation of morphofunctional characteristics of macrophages. PMID:24824795

  6. Cloning and expression of synthetic genes encoding angiotensin-I converting enzyme (ACE)-inhibitory bioactive peptides in Bifidobacterium pseudocatenulatum.

    Science.gov (United States)

    Losurdo, Luca; Quintieri, Laura; Caputo, Leonardo; Gallerani, Raffaele; Mayo, Baltasar; De Leo, Francesca

    2013-03-01

    A wide range of biopeptides potentially able to lower blood pressure through inhibition of the angiotensin-I converting enzyme (ACE) is produced in fermented foods by proteolytic starter cultures. This work applies a procedure based on recombinant DNA technologies for the synthesis and expression of three ACE-inhibitory peptides using a probiotic cell factory. ACE-inhibitory genes and their pro-active precursors were designed, synthesized by PCR, and cloned in Escherichia coli; after which, they were cloned into the pAM1 E. coli-bifidobacteria shuttle vector. After E. coli transformation, constructs carrying the six recombinant clones were electrotransferred into the Bifidobacterium pseudocatenulatum M115 probiotic strain. Interestingly, five of the six constructs proved to be stable. Their expression was confirmed by reverse transcription PCR. Furthermore, transformed strains displayed ACE-inhibitory activity linearly correlated to increasing amounts of cell-free cellular lysates. In particular, 50 μg of lysates from constructs pAM1-Pro-BP3 and pAM1-BP2 showed a 50% higher ACE-inhibitory activity than that of the controls. As a comparison, addition of 50 ng of Pro-BP1 and Pro-BP3 synthetic peptides to 50 μg of cell-free extracts of B. pseudocatenulatum M115 wild-type strain showed an average of 67% of ACE inhibition; this allowed estimating the amount of the peptides produced by the transformants. Engineering of bifidobacteria for the production of biopeptides is envisioned as a promising cell factory model system. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  7. Inhibitory effects of meju prepared with mixed starter cultures on azoxymethane and dextran sulfate sodium-induced colon carcinogenesis in mice

    Directory of Open Access Journals (Sweden)

    Ji-Kang Jeong

    2012-01-01

    Full Text Available Backgrounds: Meju is the main ingredient and the starter culture of traditional Korean fermented soybean foods; these fermented soybean products are well-known for their various health benefits, including anticancer effects. We developed the grain-type meju using probiotic mixed starter cultures to improve the qualities and functionalities of fermented soybean products, as well as the meju itself. In this study, the inhibitory effects of the grain-type meju were investigated in azoxymethane (AOM and dextran sulfate sodium (DSS-induced colon carcinogenesis mice model. Materials and Methods: AOM and DSS colon carcinogenesis was induced in female C57BL/6 mice and meju was orally administered for 4 weeks. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the levels of inflammation- and apoptosis-related genes in colonic tissue were also analyzed. Results: The administration of meju using probiotic mixed starter cultures ameliorated the symptoms of colon cancer and reduced number of neoplasia, and reduced serum proinflammatory cytokine levels and iNOS and COX-2 expression levels in colonic tissue. It increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in colonic tissues. Conclusion: The meju showed inhibitory effects on the progression of colon cancer induced by AOM and DSS by ameliorating the symptoms of colon cancer, reducing the number of neoplasias and regulating proinflammatory cytokine levels and the expressions of inflammation- and apoptosis-related genes in the colonic tissue.

  8. Baicalein inhibits IL-1β- and TNF-α-induced inflammatory cytokine production from human mast cells via regulation of the NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Krishnaswamy Guha

    2007-11-01

    Full Text Available Abstract Background Human mast cells are multifunctional cells capable of a wide variety of inflammatory responses. Baicalein (BAI, isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi, has been shown to have anti-inflammatory effects. We examined its effects and mechanisms on the expression of inflammatory cytokines in an IL-1β- and TNF-α-activated human mast cell line, HMC-1. Methods HMC-1 cells were stimulated either with IL-1β (10 ng/ml or TNF-α (100 U/ml in the presence or absence of BAI. We assessed the expression of IL-6, IL-8, and MCP-1 by ELISA and RT-PCR, NF-κB activation by electrophoretic mobility shift assay (EMSA, and IκBα activation by Western blot. Results BAI (1.8 to 30 μM significantly inhibited production of IL-6, IL-8, and MCP-1 in a dose-dependent manner in IL-1β-activated HMC-1. BAI (30 μM also significantly inhibited production of IL-6, IL-8, and MCP-1 in TNF-α-activated HMC-1. Inhibitory effects appear to involve the NF-κB pathway. BAI inhibited NF-κB activation in IL-1β- and TNF-α-activated HMC-1. Furthermore, BAI increased cytoplasmic IκBα proteins in IL-1β- and TNF-α-activated HMC-1. Conclusion Our results showed that BAI inhibited the production of inflammatory cytokines through inhibition of NF-κB activation and IκBα phosphorylation and degradation in human mast cells. This inhibitory effect of BAI on the expression of inflammatory cytokines suggests its usefulness in the development of novel anti-inflammatory therapies.

  9. Cytokine concentration in aqueous humor of eyes with diabetic macular edema.

    Science.gov (United States)

    Jonas, Jost B; Jonas, Rahul A; Neumaier, Michael; Findeisen, Peter

    2012-01-01

    of placenta growth factor (P < 0.001; ρ = 0.78), plasminogen activator inhibitor 1 (P = 0.001; ρ = 0.54), ICAM-1 (P < 0.001; ρ = 0.47), monokine induced by interferon gamma (P = 0.004; ρ = 0.44), monocyte chemoattractant protein-1 (P = 0.003; ρ = 0.43), vascular cell adhesion molecule (P = 0.01; ρ = 0.38), IL-6 (P = 0.02; ρ = 0.35), IL-8 (P = 0.02; ρ = 0.37), epidermal growth factor (P = 0.01; ρ = 0.39), and macrophage migration inhibitory factor (P = 0.01; ρ = 0.37). Numerous cytokines are associated with the presence and the amount of diabetic macular edema. Among these cytokines, ICAM-1 was the most significantly associated with the disease parameters.

  10. Development of specific cytokine and Chemokine ELISAs for Bottlenose Dolphins

    Science.gov (United States)

    Earlier detection of changes in the health status of bottlenose dolphins (Tursiops truncatus) is expected to further improve their medical care. Cytokines and chemokines are critical mediators of the cellular immune response, and studies have suggested that these molecules may serve as important bio...

  11. Targeting Integrin-β1 Impedes Cytokine-Induced Osteoclast ...

    African Journals Online (AJOL)

    but not in RANKL pathway. Given that, inflammatory cytokine secretions such as TNF-α are progressively implicated in pathological osteolysis, targeting this pathway may .... RANKL or TNF-alpha treated culture systems ... universal PCR Master Mix (Life Technologies,. USA). ... and developed using Super Signal West Dura.

  12. PORCINE CYTOKINE RESPONSES TO PAMP-STRUCTURES IN VITRO

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Skovgaard, Kerstin; Vorsholt, Henriette

    Pathogen-associated molecular patterns (PAMPs) are conserved microbial structures recognized by pattern-recognition receptors (PRRs) of the innate immune system. Binding of PAMPs by certain PRRs on dendritic cells induces these to express costimulatory molecules and cytokines, enabling an inducti...

  13. Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

    Science.gov (United States)

    Li, Zebin; Li, Ting

    2018-02-01

    Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

  14. Selective suppression of endothelial cytokine production by progesterone receptor.

    Science.gov (United States)

    Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

    2013-01-01

    Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks.

    Science.gov (United States)

    Domingues, Catarina; da Cruz E Silva, Odete A B; Henriques, Ana Gabriela

    2017-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β -amyloid aggregation. Additionally, cytokines and chemokines can influence kinases' activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several therapeutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration. This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  17. Cytokines in Male Fertility and Reproductive Pathologies: Immunoregulation and Beyond

    Directory of Open Access Journals (Sweden)

    Kate L. Loveland

    2017-11-01

    Full Text Available Germline development in vivo is dependent on the environment formed by somatic cells and the differentiation cues they provide; hence, the impact of local factors is highly relevant to the production of sperm. Knowledge of how somatic and germline cells interact is central to achieving biomedical goals relating to restoring, preserving or restricting fertility in humans. This review discusses the growing understanding of how cytokines contribute to testicular function and maintenance of male reproductive health, and to the pathologies associated with their abnormal activity in this organ. Here we consider both cytokines that signal through JAKs and are regulated by SOCS, and those utilizing other pathways, such as the MAP kinases and SMADs. The importance of cytokines in the establishment and maintenance of the testis as an immune-privilege site are described. Current research relating to the involvement of immune cells in testis development and disease is highlighted. This includes new data relating to testicular cancer which reinforce the understanding that tumorigenic cells shape their microenvironment through cytokine actions. Clinical implications in pathologies relating to local inflammation and to immunotherapies are discussed.

  18. Cytokine response to Escherichia coli in gnotobiotic pigs

    Czech Academy of Sciences Publication Activity Database

    Šplíchal, Igor; Šplíchalová, Alla; Trebichavský, Ilja

    2008-01-01

    Roč. 53, č. 2 (2008), s. 161-164 ISSN 0015-5632 R&D Projects: GA ČR GA523/05/0249 Institutional research plan: CEZ:AV0Z50200510 Keywords : germ-free pigs * escherichia coli * cytokine response Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  19. Effects of prebiotics on immune system and cytokine expression.

    Science.gov (United States)

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Navidshad, Bahman; Liang, Juan Boo

    2017-02-01

    Nowadays, use of prebiotics as feed and food additives has received increasing interest because of the beneficial effects of prebiotics on the health of animals and humans. One of the beneficial effects of prebiotics is stimulation of immune system, which can be direct or indirect through increasing population of beneficial microbes or probiotics, especially lactic acid bacteria and bifidobacteria, in the gut. An important mechanism of action of probiotics and prebiotics, by which they can affect the immune system, is changing the expression of cytokines. The present review tried to summarize the findings of studies that investigated the effects of prebiotics on immune system with focusing on their effects on cytokine expression. Generally, most of reviewed studies indicated beneficial effects for prebiotics in terms of improving immune system, by increasing the expression of anti-inflammatory cytokines, while reducing the expressions of proinflammatory cytokines. However, most of studies mainly considered the indirect effects of prebiotics on the immune system (through changing the composition and population of gut microbiota), and their direct effects still need to be further studied using prebiotics with different degree of polymerization in different hosts.

  20. The presence of cytokines in Langerhans' cell histiocytosis

    NARCIS (Netherlands)

    deGraaf, JH; Tamminga, RYJ; DamMeiring, A; Kamps, WA; Timens, W

    1996-01-01

    Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and pathogenesis of LCH are unknown; it is suggested that LCH is caused by an immunological dysregulation. Production of cytokines is a central

  1. Mouse cytokine profile skewed towards Th2 in pregnancy during ...

    African Journals Online (AJOL)

    The two classes of cytokines Th1 and Th2 determine the type of immune response elicited. The Th2 immune response is associated with successful pregnancy. Brucellosis is an intracellular bacterium that elicits the Th1 response and is known to cause spontaneous abortion in mammalian species. This study sought to ...

  2. Cisplatin ototoxicity involves cytokines and STAT6 signaling network

    Institute of Scientific and Technical Information of China (English)

    Hyung-Jin Kim; Jeong-Dug Sul; Channy Park; Sang-Young Chung; Sung-Kyun Moon; David J Lim; Hong-Seob So; Raekil Park; Gi-Su Oh; Jeong-Han Lee; Ah-Ra Lyu; Hye-Min Ji; Sang-Heon Lee; Jeho Song; Sung-Joo Park; Yong-Ouk You

    2011-01-01

    We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type,WT) and STAT4-/-,but not in STAT6-/- mice. Moreover,the expression levels of the protein and mRNA of proinflammatory cytokines,including TNF-α,IL-1β,and IL-6,were markedly increased in the serum and cochlea of WT and STAT4+,but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-/- mice were intact after treatment with cisplatin,whereas those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells,and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

  3. Cytokine production by porcine mononuclear leukocytes stimulated by mitogens

    Czech Academy of Sciences Publication Activity Database

    Rašková, G.; Kovářů, František; Bártová, J.

    2005-01-01

    Roč. 74, - (2005), s. 521-525 ISSN 0001-7213 R&D Projects: GA ČR GA524/05/0267 Institutional research plan: CEZ:AV0Z50450515 Keywords : cytokine * ELISpot * mitogen Subject RIV: ED - Physiology Impact factor: 0.353, year: 2005

  4. A BACTERIAL CYTOKINE Mukamolova et al (1998) PNAS, 95, 8916 ...

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. A BACTERIAL CYTOKINE Mukamolova et al (1998) PNAS, 95, 8916-8921. To grow or not to grow is a social decision. A resuscitation promoting factor (rpf) identified. The rpf protein shares similarity with M. tuberculosis and M. leprae ...

  5. Impact of weight loss on oxidative stress and inflammatory cytokines ...

    African Journals Online (AJOL)

    Background: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating ...

  6. Cytokine profiles in localized scleroderma and relationship to clinical features.

    Science.gov (United States)

    Kurzinski, Katherine; Torok, Kathryn S

    2011-08-01

    Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future. Published by Elsevier Ltd.

  7. Aspergillus fumigatus conidial melanin modulates host cytokine response.

    NARCIS (Netherlands)

    Chai, L.; Netea, M.G.; Sugui, J.; Vonk, A.G.; Sande, W.W. van de; Warris, A.; Kwon-Chung, K.J.; Kullberg, B.J.

    2010-01-01

    Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine

  8. Cytokine gene polymorphisms and their association with cervical ...

    African Journals Online (AJOL)

    Materials and methods: The present study was undertaken to evaluate association of cytokine gene polymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms (SNPs) viz. IL 6-597G/A (rs1800797), IL-1b-511C/T (rs16944) and TNF-a-308G/A (rs1800629) was carried out ...

  9. Impact of genetic polymorphisms of four cytokine genes on treatment ...

    African Journals Online (AJOL)

    Background: Many factors contribute for viral clearance and response to antiviral therapy. Genetic polymorphisms of cytokines, chemokines, and their receptors can alter the immune response against Hepatitis C virus (HCV). Aim of the study: The aim of the current study is to assess single nucleotide polymorphism (SNP) in ...

  10. Inflammatory Cytokines and Sleep Disturbance in Patients with Temporomandibular Disorders.

    Science.gov (United States)

    Park, Ji Woon; Chung, Jin Woo

    2016-01-01

    To assess the degree and interrelationship of sleep disturbance and plasma cytokine levels in temporomandibular disorder (TMD) pain patients. Forty female TMD patients and 20 age-, sex-, and body mass index (BMI)-matched healthy subjects were enrolled. TMD was diagnosed using the Research Diagnostic Criteria for TMD. The TMD patients were classified as having low or high disability according to Graded Chronic Pain Scale findings. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality. Plasma concentrations of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured from blood samples collected between 9 am and noon. Statistical analyses included Kruskal-Wallis and one-way analysis of variance tests to compare results between different groups and multivariate general linear models to evaluate the effect of sleep status on cytokine levels. The high-disability group had the highest PSQI and ESS scores (P disability group exhibiting the highest values (P ≤ .001). The plasma cytokine levels were significantly correlated with PSQI scores (P disability level after adjusting for both sleep indices (both P disability, had elevated plasma cytokine levels and increased ESS and PSQI scores suggestive of sleep disturbance.

  11. Neonatal levels of cytokines and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Mortensen, Erik L

    2012-01-01

    The aim of the study was to analyze cytokine profiles in neonatal dried blood samples (n-DBSS) retrieved from The Danish Newborn Screening Biobank of children developing Autism Spectrum Disorders (ASD) later in life and controls. Samples of 359 ASD cases and 741 controls were analyzed using Luminex...

  12. Clinical Application of Growth Factors and Cytokines in Wound Healing

    Science.gov (United States)

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2016-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies and future research possibilities. In this review we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. PMID:24942811

  13. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

  14. Oral warfarin intake affects skin inflammatory cytokine responses in rats.

    Science.gov (United States)

    Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Science.gov (United States)

    Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  16. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  17. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified...

  18. Cytokines, Type 2 DM and the Metabolic Syndrome | Ogbera ...

    African Journals Online (AJOL)

    comparable in the DM subjects with and without the Mets and also comparable in obese DM and non obese DM subjects. Of the Mets defining criteria, waist circumference (WC) and Triglyceride (TG) were found to be significantly associated with only two of the studied cytokines. The correlation coefficient and p values of ...

  19. Albumin synthesis in protein energy malnutrition

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, C; Hardy, S; Kleinman, R E [Harvard Medical School, Boston, MA (United States); Lembcke, J [Instituto de Investigacion Nutricional, La Molina, Lima (Peru); Young, V E [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Lab. of Human Nutrition

    1994-12-31

    The dietary treatment of protein-energy malnutrition (PEM) has been designed on an empirical basis, with outcomes for successful management including body weight gain and resolution of apathy. We propose using the measurements of protein synthesis as a more objective measure of renourishment. We will therefore randomize a group of malnourished children (weigh-for-height Z score <-2.0) to receive either a standard (10% of calories as protein) or increased (15%) amount of dietary protein early in their recovery phase. We will calculate albumin synthesis rates via the flooding dose technique, using {sup 13}C-leucine and serial measurements of {sup 13}C-enrichment of albumin. Isotope infusions will be performed on days one and three, following a standard three hour fast. Since albumin synthesis is reduced under the influence of cytokines which mediate the inflammatory response, results will be stratified according to the presence or absence of clinically apparent infections. We hypothesize that the provision of added dietary protein will optimize albumin synthesis rates in PEM as well as attenuate the reduction in albumin synthesis seen in the presence of infections. (author). 20 refs.

  20. Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma

    Directory of Open Access Journals (Sweden)

    Jolanta Budzyńska-Włodarczyk

    2016-02-01

    Full Text Available Introduction : Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. Aim: To determine concentrations of interleukin (IL-27, transforming growth factor (TGF-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. Material and methods: The study encompassed 17 females with localized scleroderma (aged 25–67. The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. Results : The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. Conclusions : The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

  1. Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma.

    Science.gov (United States)

    Budzyńska-Włodarczyk, Jolanta; Michalska-Jakubus, Małgorzata M; Kowal, Małgorzata; Krasowska, Dorota

    2016-02-01

    Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. To determine concentrations of interleukin (IL)-27, transforming growth factor (TGF)-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. The study encompassed 17 females with localized scleroderma (aged 25-67). The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

  2. Distinctive in vitro effects of T-cell growth cytokines on cytomegalovirus-stimulated T-cell responses of HIV-infected HAART recipients

    International Nuclear Information System (INIS)

    Patterson, Julie; Jesser, Renee; Weinberg, Adriana

    2008-01-01

    Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the γ-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting effect of IL-2 and IL-15 on proliferation correlated with their ability to prevent late apoptosis. However, IL-2 increased the frequency of cells in early apoptosis, whereas IL-15 increased the frequency of fully viable cells. Both IL-2 and IL-15 increased cytomegalovirus-induced CD4 + and CD8 + T-cell proliferation and the synthesis of Th1 and pro-inflammatory cytokines and chemokines. However, only IL-2 increased the frequency of regulatory T cells and Th2 cytokine production, both of which have the potential to attenuate antiviral immune responses. Overall, compared to other γ-chain cytokines, IL-15 had the most favorable profile for boosting antiviral cell-mediated immunity

  3. Cytokine modulation by stress hormones and antagonist specific hormonal inhibition in rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) head kidney primary cell culture.

    Science.gov (United States)

    Khansari, Ali Reza; Parra, David; Reyes-López, Felipe E; Tort, Lluís

    2017-09-01

    A tight interaction between endocrine and immune systems takes place mainly due to the key role of head kidney in both hormone and cytokine secretion, particularly under stress situations in which the physiological response promotes the synthesis and release of stress hormones which may lead into immunomodulation as side effect. Although such interaction has been previously investigated, this study evaluated for the first time the effect of stress-associated hormones together with their receptor antagonists on the expression of cytokine genes in head kidney primary cell culture (HKPCC) of the freshwater rainbow trout (Oncorhynchus mykiss) and the seawater gilthead sea bream (Sparus aurata). The results showed a striking difference when comparing the response obtained in trout and seabream. Cortisol and adrenocorticotropic hormone (ACTH) decreased the expression of immune-related genes in sea bream but not in rainbow trout and this cortisol effect was reverted by the antagonist mifepristone but not spironolactone. On the other hand, while adrenaline reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6) in rainbow trout, the opposite effect was observed in sea bream showing an increased expression (IL-1β, IL-6). Interestingly, this effect was reverted by antagonist propranolol but not phentolamine. Overall, our results confirm the regional interaction between endocrine and cytokine messengers and a clear difference in the sensitivity to the hormonal stimuli between the two species. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cytokine profile of rats fed a diet containing shrimp

    Directory of Open Access Journals (Sweden)

    Elizabeth Lage Borges

    2013-02-01

    Full Text Available OBJECTIVE: Studies have shown that shrimps reduced the tensile strength of scars in rat skin. The aim of the present study was to assess the cytokine profile of rats fed shrimp. METHODS: Group 1 (control received a regular diet and Group 2 (experimental received a diet containing 33% shrimp for nine days. The two diets contained the same amounts of proteins, fats and carbohydrates. Serum cytokine levels were determined by ELISA and a segment of the jejunum was taken to investigate its histological morphology and eosinophil infiltrate. RESULTS: The experimental group had lower serum levels of interleukin-4 (IL-4 (14.4±1.9 versus 18.11±2.6pg/mL; p<0.05 and IL-10 (5.0±0.98 versus 7.5±1.2pg/mL; p<0.05 and higher levels of IL-6 (17.8±2.3 versus 3.2±0.4pg/mL, p<0.001 than controls. Morphologically, the shrimp-based diet caused an architectural disorganization of the intestinal mucosa and a greater amount of eosinophils in the jejunal villus. CONCLUSION: Our data suggests that shrimp consumption leads to a significant increase in the cytokine IL-6, a decrease in the immunomodulatory cytokine IL-10 in the serum of rats, and high eosinophil infiltration in the jejunum. The cytokine profile typical of inflammation and the histological aspect of the jejunum are compatible with food allergy.

  5. Serum cytokine profile in the subclinical form of visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Gama M.E.A.

    2004-01-01

    Full Text Available The factors determining the development or not of visceral leishmaniasis (VL have not been completely identified, but a Leishmania-specific cellular immune response seems to play a fundamental role in the final control of infection. Few studies are available regarding the production of cytokines in the subclinical form of VL, with only the production of IFN-g and TNF-a known. The aim of the present study was to identify immunological markers for the oligosymptomatic or subclinical form of VL. A prospective cohort study was conducted on 784 children aged 0 to 5 years from an endemic area in the State of Maranhão, Brazil, between January 1998 and December 2001. During 30 consecutive months of follow-up, 33 children developed the oligosymptomatic form of the disease and 12 the acute form. During the clinical manifestations, serum cytokine levels were determined in 27 oligosymptomatic children and in nine patients with the acute form using a quantitative sandwich enzyme immunoassay. In the subclinical form of VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in 85.2%, IFN-g in 48.1%, IL-10 in 88.9%, and TNF-a in 100.0%, with the last two cytokines showing significantly lower levels than in the acute form. IL-4 was not detected in oligosymptomatic individuals. Multiple discriminant analysis used to determine the profile or combination of cytokines predominating in the subclinical form revealed both a Leishmania resistance (Th1 and susceptibility (Th2 profile. The detection of both Th1 and Th2 cytokine profiles explains the self-limited evolution accompanied by the discrete alterations observed for the subclinical form of VL.

  6. The Interleukin-20 Cytokine Family in Liver Disease

    Directory of Open Access Journals (Sweden)

    Esther Caparrós

    2018-05-01

    Full Text Available The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ. The best-studied member of the family in inflammatory balance of the liver is the IL-22 cytokine, which on the one hand may have a protective role in fibrosis progression but on the other may induce liver tissue susceptibility in hepatocellular carcinoma development. Other members of the family might also carry out this dual function, as some of them share IL receptor subunits and signal through common intracellular pathways. Investigators are starting to consider the potential for targeting IL-20 subfamily members in liver disease. The recently explored role of miRNA in the transcriptional regulation of IL-22 and IL-24 opens the door to promising new approaches for controlling the local immune response and limiting organ injury. The IL-20RA cytokine receptor has also been classified as being under miRNA control in non-alcoholic steatohepatitis. Moreover, researchers have proposed combining anti-inflammatory drugs with IL-22 as a hepatoprotective IL for alcoholic liver disease (ALD treatment, and clinical trials of ILs for managing severe alcoholic-derived liver degeneration are ongoing. In this review, we focus on exploring the role of the IL-20 subfamily of cytokines in viral hepatitis, ALD, non-alcoholic steatohepatitis, and hepatocellular carcinoma, as well as delineating the main strategies explored so far in terms of therapeutic possibilities of the IL-20 subfamily of cytokines in liver disease.

  7. Serum Profiles of Cytokines in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Alireza Sadeghi

    2017-05-01

    Full Text Available Introduction: Behcet’s disease (BD is a chronic systemic autoinflammatory vasculitis which is handled by the variety of proteins like cytokines. Therefore, cytokines are considered as one of the prototypic factors during inflammatory responses of BD. Consequently, the present study was designed for evaluation of cytokine profiles in Iranian BD cases, including those with and without uveitis. Materials and Method: All cases were divided into three groups based on ophthalmologic exam results: BD with uveitis, BD without uveitis, and recovered uveitis BD. Cases with a history of BD recovery were placed in the group of recovered uveitis. The patients with infectious uveitis as well as other collagen vascular diseases and patients who have used biologics to treat ocular immune-mediated diseases were excluded. Finally, after venous blood sampling, levels of cytokines were quantified and statistical approaches were performed for measurements. Results: Enrolled cases were divided to 26 patients with active uveitis, 25 patients with recovered uveitis and 24 patients without uveitis and interestingly, just IL-2 was the only cytokine that showed statistical difference in patients with BD uveitis in comparison with other groups (pvalue = 0.02. The pair wise comparison showed a significant difference between the patients with and without uveitis groups (pvalue = 0.004 as well as patients with uveitis and recovered uveitis groups (pvalue = 0.002. Discussion: Significant elevation of IL-2 in patients with uveitis (in comparison with recovered or without uveitis cases demonstrates that it may be one of the main proteins that enroll in the pathophysiology of BD uveitis and may be considered as a new target for refractory disease therapies. Studies with larger samples can help to obtain more accurate conclusions.

  8. Cytokines in chronically critically ill patients after activity and rest.

    Science.gov (United States)

    Winkelman, Chris; Higgins, Patricia A; Chen, Yea Jyh Kathy; Levine, Alan D

    2007-04-01

    Inflammation, a common problem for patients in the intensive care unit (ICU), frequently is associated with serious and prolonged critical illnesses. To date, no study has examined whether physical activity influences inflammatory factors in critically ill adults. The objectives of this study were to (a) examine the relationships between type and duration of physical activity and serum levels of interleukin 6 (IL-6), a proinflammatory cytokine; IL-10, an anti-inflammatory cytokine; and their ratio and (b) determine if there are associations between cytokines or their ratio and activity or outcomes. This descriptive feasibility study investigated the approaches to measuring levels of physical activity and its relationship to serum levels of IL-6 and IL-10 and the ratio between them in patients with prolonged mechanical ventilation during periods of activity and rest. Measurements included serum IL-6 and IL-10 levels, direct observation and actigraphy, and prospective chart review. Ten critically ill patients who were mechanically ventilated for an average of 10 days in a large, urban, teaching hospital were enrolled. The average ratio of IL-6 to IL-10 improved after an average of 14.7 min of passive physical activity, typically multiple in-bed turns associated with hygiene. IL-6, IL-10, and their ratio were not associated with patient outcomes of weaning success or length of stay. High levels of IL-6 were associated with mortality. Cytokine balance may be improved by low levels of activity among patients with prolonged critical illness. The pattern of cytokines produced after activity may improve patients' recovery from prolonged critical illness and mechanical ventilation.

  9. Minimum inhibitory concentration values and problematic disk break ...

    African Journals Online (AJOL)

    Latife Ä°ÅŸeri

    2015-08-08

    Aug 8, 2015 ... to tigecycline, and to test the correlation between the minimal inhibitory concentration (MIC) and ... This study was performed using 108 strains of enterococci. The .... drugs (TetA-E, TetK) from inside the bacterial cell, and ribo-.

  10. Assessment of inhibitory substances in the seed coat of some ...

    African Journals Online (AJOL)

    Laboratory experiment was conducted at the Faculty of Agriculture and Veterinary Medicine, Imo State University, Nigeria to assess the inhibitory substances in the seed coat of 15 cowpea cultivars for resistance against Callosobruchus maculatus. Fifty (50) seeds of the cowpea cultivars were collected from the International ...

  11. Experimental study on the inhibitory effect of sodium cantharidinate ...

    African Journals Online (AJOL)

    Backgroud: Cantharidin, and its derivatives can not only inhibit the proliferation of tumor cells, but can also induce tumor cell apoptosis. It shows cantharidin exhibits a wide range of reactivity in anticancer. The objective of this paper was to study the inhibitory effect of sodium cantharidinate on human hepatoma HepG2 cells.

  12. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian

    2015-01-01

    INTRODUCTION: Members of the interleukin-6 (IL-6) family, IL-6 and ciliary neurotrophic factor (CNTF) have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well...

  13. Immune inhibitory receptors in viral infection and cancer

    NARCIS (Netherlands)

    Karnam, G.

    2014-01-01

    We are protected from external and internal dangers by our immune system. Immune responses need to be balanced to prevent uncontrolled inflammation and/or autoimmunity. Cell growth inhibition, apoptosis, and down regulation of receptor signals are all part of the inhibitory tools used by the immune

  14. Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

    DEFF Research Database (Denmark)

    Saito, Fumiji; Hirayasu, Kouyuki; Satoh, Takeshi

    2017-01-01

    , but the immune regulatory mechanisms used by P. falciparum remain largely unknown. Here we show that P. falciparum uses immune inhibitory receptors to achieve immune evasion. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150-200 genes per parasite genome...

  15. Sleep: The hebbian reinforcement of the local inhibitory synapses.

    Science.gov (United States)

    Touzet, Claude

    2015-09-01

    Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency – just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS – because it only allows local neural activation – decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Effect of partially purified angiotensin converting enzyme inhibitory ...

    African Journals Online (AJOL)

    This study evaluated the effect of partially-purified angiotensin converting enzyme (ACE) inhibitory proteins obtained from the leaves of Moringa oleifera on blood glucose, serum ACE activity and lipid profile of alloxaninduced diabetic rats. Twenty-five apparently healthy male albino rats were divided into five groups of five ...

  17. Conflict Inhibitory Control Facilitates Pretense Quality in Young Preschoolers

    Science.gov (United States)

    Van Reet, Jennifer

    2015-01-01

    The present research explores the role of inhibitory control (IC) in young preschoolers' pretense ability using an ego depletion paradigm. In Experiment 1 (N = 56), children's pretense ability was assessed either before or after participating in conflict IC or control tasks, and in Experiment 2 (N = 36), pretense ability was measured after…

  18. Effect of Bacteriocin-like Inhibitory Substances Produced by Vaginal ...

    African Journals Online (AJOL)

    Reduction of vaginal Lactobacillus population leads to overgrowth of opportunistic organisms such as Streptococcus agalactiae (Group B Streptococcus, GBS), which causes life threatening neonatal infections. The activities of bacteriocin-like inhibitory substances (BLIS) produced by Lactobacillus species isolated from the ...

  19. α-Glucosidase inhibitory hydrolyzable tannins from Eugenia jambolana seeds.

    Science.gov (United States)

    Omar, Raed; Li, Liya; Yuan, Tao; Seeram, Navindra P

    2012-08-24

    Three new hydrolyzable tannins including two gallotannins, jamutannins A (1) and B (2), and an ellagitannin, iso-oenothein C (3), along with eight known phenolic compounds were isolated from the seeds of Eugenia jambolana fruit. The structures were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for α-glucosidase inhibitory effects compared to the clinical drug acarbose.

  20. Evaluation of Apoptotic and Growth Inhibitory Activity of Phloretin in ...

    African Journals Online (AJOL)

    Results: The results show that the inhibitory activity of phloretin in BGC823 gastric cancer cells was mediated by induction of apoptosis ... anti-proliferative effects of phloretin was dose-dependent and inhibited the growth of BGC823 gastric cancer cells by 73 % at 30 μM; .... weeks at 37 °C in 5 % CO2 in humidified incubator.