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Sample records for assessing inflammatory response

  1. Exposure Assessment and Inflammatory Response Among Workers Producing Calcium Carbonate Nanomaterials

    Science.gov (United States)

    Cui, Ling

    . Modification is thought to be the primary emission source. It is discovered nanoparticles in the size range of 20-300nm dominate in this workplace, which consists of 90-98% of particle counts in the respirable fraction. Based on the sampling results from 2012, there was a strong relationship between number concentration in 5-25um range and the respirable mass concentration (r= 0.908); however, no such correlation was found between number concentration in nanoscale and respirable mass (r= 0.018). The deposited surface area in TB (r=0.66) and alveolar region (r=0.46) was modestly correlated with number concentration of particles in the nanoscale. A reduced FEV1 and increased BP were consistently found among medium-mass exposure compared to low-mass exposure, however no statistical significance was found. When comparing the four exposure metrics, we found number concentration and surface area concentration in general produce effects in similar direction, however opposite to mass concentration. Such observation is consistent with the correlation among these exposure metrics. Airway inflammatory responses presented a dose-response relationship using mass as exposure metric. The concentrations of IL1beta (p =0.043) and IL8 (p=0.008) in sputum among high mass-exposure group were statistically greater than that in low-mass exposure group. It suggested the inflammatory responses were associated with mass concentration of inhaled nanoparticle particles, which are mainly made up by agglomerated form of nanoparticles. At current stage, with limited understanding of the toxicological perspective of nanoparticle, a complete exposure assessment in nanoparticle facility needs to be conducted in both bulk- and nano-form.

  2. Assessment of clinical and laboratory parameters that reflect inflammatory response and organ function in sepsis

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    Herdiman T. Pohan

    2005-03-01

    Full Text Available Sepsis is a spectrum of clinical conditions caused by the host immune response to infection or other inflammatory stimuli characterized by systemic inflammation. Clinical response to sepsis could be varies according to compensate or decompensate state, inflammatory process and host condition. Aims of this study is to assess the role of some parameters (clinical and biochemical, hematology, arterial blood gas analysis and coagulation in supporting the diagnosis of sepsis. A cross-sectional study was performed in the Internal Medicine Inpatient Unit of Dr. Cipto Mangunkusumo National General Hospital, Jakarta, from February to July 2002. Forty-two patients who fulfilled the criteria of sepsis, severe sepsis, and septic shock were enrolled in this study. Clinical details and blood specimens for hematological, biochemical, arterial blood gas analysis and coagulation were collected. There were 42 subjects who participated in the study, aged from 19 to 78 years old. Eleven subjects fulfilled the criteria for early sepsis, 20 severe sepsis and 11 septic shock. Clinical examination showed that the Glasgow coma scale (GCS was significantly reduced in severe sepsis and septic shock. Heart rate, respiration rate and body temperature were increased in all groups. Hemoglobin levels mostly below 10 g/dl and hematocrite levels below 30 %. The leucocyte counts were increased in more than 80%, mostly above 15.000/mm3. The platelet count were low (below 50.000/mm3 especially in septic shock.  The serum creatinine were significantly increased (>2 mg/dl in severe sepsis and septic shock. Albumin was decreased,  lactate dehydrogenase/LDH and procalcitonin  were increased. The arterial blood gas analysis showed that: pH and HCO3 were decreased especially in  septic shock; the PO2 was lower in severe sepsis and septic shock; and PCO2 was below 32 mmHg in all groups. Coagulation examinations showed that fibrinogen was significantly decreased in septic shock; PT and

  3. Systemic inflammatory response syndrome (SIRS)

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    Balk, Robert A

    2014-01-01

    The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition. PMID:24280933

  4. Transcompartmental inflammatory responses in humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A;

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...... measured. MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p ...-α, interleukin-6, and albumin (all p inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α. CONCLUSIONS: Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential...

  5. Development of an experimental model for assessing the effects of cigarette smoke and virus infections on inflammatory responses to bacterial antigens.

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    Moscovis, Sophia; Hall, Sharron; Burns, Christine; Scott, Rodney; Blackwell, Caroline

    2014-08-01

    Interactions among major risk factors associated with bacterial infections were assessed in a model system using surrogates for virus infection; IFN-g, and exposure to cigarette smoke; cigarette smoke extract (CSE), nicotine and cotinine. Cytokine responses elicited by LPS from THP-1 cells in the presence of these components, or combinations of components, were assessed by multiplex bead assay, i.e. IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ. IFN-γ-priming significantly increased pro-inflammatory cytokines induced by LPS. CSE suppressed production of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ, but enhanced production of IL-8. Nicotine and cotinine suppressed all cytokine responses. In combination, IFN-γ masked the inhibitory effects of CSE. In relation to the objectives of the study, we concluded that (a) IFN-γ at biologically relevant concentrations significantly enhanced pro-inflammatory responses; (b) CSE, nicotine and cotinine dysregulated the inflammatory response and that the effects of CSE were different from those of the individual components, nicotine and cotinine; (c) when both IFN-γ and CSE were present, IFN-γ masked the effect of CSE. There is a need for clinical investigations on the increase in IL-8 responses in relation to exposure to cigarette smoke and increased pro-inflammatory responses in relation to recent viral infection. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  6. Inflammatory response related scoring systems in assessing the prognosis of patients with pancreatic ductal adenocarcinoma:a systematic review

    Institute of Scientific and Technical Information of China (English)

    Jawad Ahmad; Nathan Grimes; Shahid Farid; Gareth Morris-Stiff

    2014-01-01

    BACKGROUND: Various scoring systems based on assessment of the systemic inflammatory response help assessing the prognosis of patients with pancreatic ductal adenocarcinoma. In the present systematic review we evaluated the validity of four pre-intervention scoring systems: Glasgow prognostic score (GPS) and its modified version (mGPS), platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), and prognostic nutrition index (PNI). DATA SOURCES: MOOSE guidelines were followed and EMBASE and MEDLINE databases were searched for all published studies until September 2013 using comprehensive text word and MeSH terms. All identified studies were analyzed, and relevant studies were included in the systematic review. RESULTS: Six studies were identified for GPS/mGPS with 3 reporting statistical significance for GPS/mGPS on both univariate analysis (UVA) and multivariate analysis (MVA). Two studies suggested prognostic significance on UVA but not MVA, and in the final study UVA failed to show significance. Eleven studies evaluated the prognostic value of NLR. Six of them reported prognostic significance for NLR on UVA that persisted at MVA in 4 studies, and in the remaining 2 studies NLR was the only significant factor on UVA. In the remaining 5 studies, all in patients undergoing resection, there was no significance on UVA. Seven studies evaluated PLR, with only one study demonstrated its prognostic significance on both UVA and MVA, the rest did not show the significance on UVA. Of the two studies identified for PNI, one demonstrated a statistically significant difference in survival on both UVA and MVA, and the other reported no significance for PNI on UVA. CONCLUSIONS: Both GPS/mGPS and NLR may be useful but further better-designed studies are required to confirm their value. PLR might be little useful, and there are at present inadequate data to assess the prognostic value of PNI. At present, no scoring system is reliable enough to be accepted into routine use

  7. Inflammatory response and extracorporeal circulation.

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    Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander

    2015-06-01

    Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery.

  8. Inflammatory Response to Sorbent Hemodialysis.

    Science.gov (United States)

    Rosales, Laura; Thijssen, Stephan; Kruse, Anja; Sipahioglu, Murat Hairy; Hirachan, Padam; Raimann, Jochen G; Kuntsevich, Viktoriya; Carter, Mary; Levin, Nathan W; Kotanko, Peter

    2015-01-01

    Inflammation is common and associated with morbidity and mortality in hemodialysis (HD) patients. Exposure to endotoxin contained in the dialysate may trigger inflammation. Dialysate volume is substantially reduced in sorbent HD compared with standard single-pass dialysis. In this prospective study (Clinicaltrials.gov, number: NCT00788905), we compared the inflammatory response to single-pass and sorbent HD. Patients receiving single-pass HD were studied during 1 week of sorbent HD (Allient system; Renal Solutions, Warrendale, PA) and 1 week of single-pass HD. Patients were dialyzed using high-flux polysulfone dialyzers. Midweek pre- and post-HD serum levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, interferon gamma, tumor necrosis factor alpha (TNF-α), and eotaxin were determined and their intradialytic change corrected for hemoconcentration during single-pass HD and sorbent HD compared by paired t-test. We enrolled 18 patients, nine completed the study. Although TNF-α decreased during both single-pass and sorbent HD (p < 0.001), none of the other biomarkers changed significantly during HD. We observed no difference between single-pass and sorbent HD. For the markers investigated in this study, there was no difference in the acute intradialytic inflammatory response to single-pass or sorbent HD.

  9. Markers of systemic inflammatory response in coxarthrosis

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    Korshunov G.V.

    2013-12-01

    Full Text Available Objective: to detect markers of the systemic inflammatory response syndrome in patients with coxarthrosis by means of assessment of the status of the hemostasis system, endothelium function and inflammation intensity. Material and Methods. The indices of the plasmatic hemostasis, levels of VCAM-1, ICAM-1, ELAM-1, VEGF-A, neop-terin were analyzed. Results. It has been found that among the patients with hip coxarthrosis a group of patients (47% with endothelium dysfunction, cellular immunity activation, a high content of Soluble Fibrin Monomer Complex and D-dimers and a group of patients (53% without any abnormalities in these parameters should be differentiated. Conclusion. Among the patients with hip coxarthrosis a group with signs of a systemic inflammatory response syndrome (occurrence of endothelium dysfunction, cellular immunity activation, a high content of Soluble Fibrin Monomer Complex and D-dimers and a group of patients with reference values of these parameters can be determined. The markers of the systemic inflammatory response syndrome in cases with hip osteoarthrosis are Soluble Fibrin Monomer Complex and D-dimers, high levels of intercellular adhesion molecule-1 (slCAM-1, vascular cell adhesion molecule-2 (sVCAM-1, cell adhesion E-selectin-1 (ELAM-1 and Neopterin (Np.

  10. Histopathological assessment and inflammatory response in the digestive gland of marine mussel Mytilus galloprovincialis exposed to cadmium-based quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Thiago Lopes [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Laboratory of Cellular Behavior, Biological Sciences Institute, Federal University of Goiás, Goiânia, Goiás (Brazil); Sabóia-Morais, Simone Maria Teixeira [Laboratory of Cellular Behavior, Biological Sciences Institute, Federal University of Goiás, Goiânia, Goiás (Brazil); Bebianno, Maria João, E-mail: mbebian@ualg.pt [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2016-08-15

    Highlights: • Digestive gland of marine mussels is target for Cd-based QDs toxicity. • Both Cd forms increase the frequency of atrophic digestive tubules in a time dependent pattern. • QDs induce higher inflammatory responses when compared to dissolved Cd. • Multiparametric tissue-levels biomarkers show distinct mode of action in the digestive gland. - Abstract: Although tissue-level biomarkers have been widely applied in environmental toxicology studies, the knowledge using this approach in marine invertebrates exposed to engineered nanomaterials (ENMs) remains limited. This study investigated histopathological alterations and inflammatory responses induced by Cd-based quantum dots (QDs), in comparison with their dissolved counterparts, in the marine mussel Mytilus galloprovincialis. Mussels were exposed to CdTe QDs and dissolved Cd at the same concentration (10 μg Cd L{sup −1}) for 14 days and a total of 15 histopathological alterations and 17 histomorphometric parameters were analysed in the digestive gland along with the determination of histopathological condition indices (I{sub h}). A multivariate analysis showed that the mussel response to QDs was more related to exposure time, inflammatory conditions (frequency of haemocytic infiltration and granulocytomas) and changes of cell-type composition (especially the rate between basophilic and digestive cells) when compared to dissolved Cd, while the response to dissolved Cd was associated with histomorphometric parameters of the epithelium and lumen of digestive tubules and increase of the atrophic tubule frequency. Both Cd forms induced higher I{sub h} compared to unexposed mussels indicating a significant decrease in the health status of digestive gland in a Cd form and time-dependent pattern. Results indicate that the multiparametric tissue-level biomarkers in the digestive gland provide a suitable approach to assess the ecotoxicity and mode of action of metal-based ENMs in marine bivalves.

  11. Short-term assessment of toxicological aspects, oxidative and inflammatory response to dietary melon superoxide dismutase in rats.

    Science.gov (United States)

    Carillon, Julie; Fouret, Gilles; Feillet-Coudray, Christine; Lacan, Dominique; Cristol, Jean-Paul; Rouanet, Jean-Max

    2013-05-01

    The protective effects of SODB, a gastro-resistant encapsulated melon superoxide dismutase, on haematological and biochemical parameters and inflammatory and oxidative status, were evaluated in the blood and liver tissue. The study consisted in a 28-day experiment on rats supplemented with three doses (10, 40 and 160USOD/day) of SODB-M, SODB-D or SODB-S, different depending on the nature of the coating (palm oil, shellac or gum Arabic respectively). No mortality, abnormal clinical signs, behavioural changes or macroscopic findings were observed whatever the groups. Haematological parameters (total red blood cell count, haemoglobin content, haematocrit, red cell indices, white blood cell count and platelets count) were not modified in SODB treated-groups. No marked change was recorded in biochemical parameters (plasma urea, creatinine, lipids, electrolytes, bilirubin, transaminases and gamma-glutamyl transferase). The liver endogenous antioxidant enzymes (copper/zinc and manganese superoxide dismutase) expressions were significantly increased in the rats receiving the highest dose of SODB (160USOD/day) whatever the coating. Moreover, interleukin-6, a marker of inflammation, was significantly decreased in these high dose-treated-groups. The present study indicates that dietary supplementation of SODB on rats has no harmful side effects and could be beneficial especially at high doses.

  12. Systemic inflammatory response following acute myocardial infarction.

    Science.gov (United States)

    Fang, Lu; Moore, Xiao-Lei; Dart, Anthony M; Wang, Le-Min

    2015-05-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI.

  13. Systemic inflammatory response following acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Lu FANG; Xiao-Lei Moore; Anthony M Dart; Le-Min WANG

    2015-01-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial in-farction, and heart failure) in patients with AMI.

  14. Transport induced inflammatory responses in horses.

    Science.gov (United States)

    Wessely-Szponder, J; Bełkot, Z; Bobowiec, R; Kosior-Korzecka, U; Wójcik, M

    2015-01-01

    Deleterious response to road transport is an important problem in equine practice. It determines different physiological, immunological and metabolic changes which lead to increased susceptibility to several disorders such as pneumonia, diarrhea, colics, laminitis, injuries and rhabdomyolisis. The aim of our study was to look for possible relationships between transportation of female young and older horses over a long and short distance and an inflammatory state reflected by an increase of acute phase protein concentration, oxidative stress and muscle injury. The study was conducted on 24 cold-blooded female horses divided into four groups. Six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 550 km, six fillies aged 6-18 months and six mares aged 10-12 years were transported over the distance of about 50 km. Plasma and serum were obtained from blood samples taken before transportation (T0), immediately after transportation (T1) and at an abattoir during slaughter (T2). In these samples fibrinogen, MDA, AST and CK were assessed. Fibrinogen increased in all studied groups especially in fillies after long distance transportation, where it reached 205±7.07 mg/dl before transportation, 625±35.35 mg/dl after transportation, and 790±14.14 mg/dl during slaughter. MDA concentrations rose after transportation and reached the maximal level during slaughter. CK activity was more elevated after short transportation in younger horses, whereas initial activity of AST was higher in older horses. We estimated that intensified responses from acute phase, oxidative stress and muscle injury parameters indicated an inflammatory state.

  15. Inflammatory response and the endothelium.

    Science.gov (United States)

    Meroni, P L; Borghi, M O; Raschi, E; Ventura, D; Sarzi Puttini, P C; Atzeni, F; Lonati, L; Parati, G; Tincani, A; Mari, D; Tedesco, F

    2004-01-01

    Antiphospholipid-mediated endothelium perturbation plays a role in antiphospholipid syndrome (APS)-associated vasculopathy. Antiphospholipid antibodies activate endothelium both in vitro and in vivo experimental models by inducing a pro-inflammatory/-coagulant phenotype; the antibodies recognize beta2 glycoprotein I (beta2GPI) on human endothelial cells (EC) from different parts of the vasculature. In spite of such large in vitro evidence, few studies have addressed the issue whether or not a comparable endothelial perturbation might be detectable in vivo. We investigated several indirect ex vivo parameters of endothelial dysfunction: plasma levels of soluble adhesion molecules (sADM), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays. The study included: patients with primary antiphospholipid syndrome (n=32), with the syndrome secondary to non-active systemic lupus erythematosus (SLE, n=10), six patients with persistent antiphospholipid positivity at medium/high titre without any clinical manifestation of the syndrome. Fifty-two age and sex matched healthy subjects have been enrolled as controls. In addition, circulating endothelial cells identified by flow cytometry and the brachial artery flow-mediated vasodilation (FMV) were evaluated in 26 patients (20 primary and 6 lupus syndromes) and 30 healthy controls. Plasma levels of soluble adhesion molecules did not differ from controls, while a significant increase in von Willebrand factor titres (P<0.05) was found. No significant difference was found regarding the number of circulating endothelial cells and flow-mediated vasodilation. As a whole, these findings do suggest that antiphospholipid antibodies per se are not able to support a full-blown endothelial perturbation in vivo. As shown in antiphospholipid syndrome experimental animal models, a two-hit hypothesis is suggested.

  16. Systemic Inflammatory Response and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    L. V. Molchanova

    2005-01-01

    Full Text Available The lecture presents the materials of foreign studies on the mechanisms responsible for the formation of a systemic inflammatory response syndrome (SIRS. The hypotheses accounting for the occurrence of SIRS in emergencies are described. Adhesion molecules (AM and endothelial dysfunction are apparent to be involved in the inflammatory process, no matter what the causes of SIRS are. The current classification of AM and adhesion cascades with altered blood flow is presented. There are two lines in the studies of AM. One line is to measure the concentration of AM in the plasma of patients with emergencies of various etiology. The other is to study the impact of antiadhesion therapy on the alleviation of the severity of terminal state and its outcome. The studies provide evidence for that an adhesive process is a peculiar prelude to a systemic inflammatory response.

  17. Mucosal Inflammatory Response to Salmonella Typhimurium Infection

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    Samir ePatel

    2014-07-01

    Full Text Available The human intestinal epithelium consists of a single layer of epithelial cells that forms a barrier against food antigens and the resident microbiota within the lumen. This delicately balanced organ functions in a highly sophisticated manner to uphold the fidelity of the intestinal epithelium and to eliminate disease-causing microorganisms. On the luminal side, this barrier is fortified by a thick mucus layer, and on the serosal side exists the lamina propria containing a resident population of immune cells. Pathogens that are able to breach this barrier disrupt the healthy epithelial lining by interfering with the regulatory mechanisms that govern the normal balance of intestinal architecture and function. This disruption results in a coordinated innate immune response deployed to eliminate the intruder that includes the release of antimicrobial peptides, activation of pattern recognition receptors, and recruitment of a variety of immune cells. In the case of Salmonella enterica serovar Typhimurium (S. Typhimurium infection, induction of an inflammatory response has been linked to its virulence mechanism, the type III secretion system (T3SS. The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response. As the role of the intestinal epithelium in initiating an immune response has been increasingly realized, this review will highlight recent research that details progress made in understanding mechanisms underlying the mucosal inflammatory response to Salmonella infection, and how such inflammatory responses impact pathogenic fitness of this organism.

  18. Natural Products: Insights into Leishmaniasis Inflammatory Response

    Science.gov (United States)

    Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

    2015-01-01

    Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

  19. Pharmacologic Strategies for Combating the Inflammatory Response

    OpenAIRE

    Landis, Clive

    2007-01-01

    The “systemic inflammatory response” is a multifaceted defensive reaction of the body to surgical trauma and cardiopulmonary bypass (CPB), characterized by systemic activation of fibrinolysis, coagulation, complement, immune cells, platelets, and oxidative pathways, all overlaid onto localized trauma to the grafted vessel or vascular beds susceptible to ischemia/reperfusion. There is going to be no single magic bullet to diminish such a broad host defense response to surgery. The best chance ...

  20. Attenuated inflammatory response in aged mice brains following stroke.

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    Matthias W Sieber

    Full Text Available BACKGROUND: Increased age is a major risk factor for stroke incidence, post-ischemic mortality, and severe and long-term disability. Stroke outcome is considerably influenced by post-ischemic mechanisms. We hypothesized that the inflammatory response following an ischemic injury is altered in aged organisms. METHODS AND RESULTS: To that end, we analyzed the expression pattern of pro-inflammatory cytokines (TNF, IL-1α, IL-1β, IL-6, anti-inflammatory cytokines (IL-10, TGFβ1, and chemokines (Mip-1α, MCP-1, RANTES of adult (2 months and aged (24 months mice brains at different reperfusion times (6 h, 12 h, 24 h, 2 d, 7 d following transient occlusion of the middle cerebral artery. The infarct size was assessed to monitor possible consequences of an altered inflammatory response in aged mice. Our data revealed an increased neuro-inflammation with age. Above all, we found profound age-related alterations in the reaction to stroke. The response of pro-inflammatory cytokines (TNF, and IL-1β and the level of chemokines (Mip-1α, and MCP-1 were strongly diminished in the aged post-ischemic brain tissue. IL-6 showed the strongest age-dependent decrease in its post-ischemic expression profile. Anti-inflammatory cytokines (TGFβ1, and IL-10 revealed no significant age dependency after ischemia. Aged mice brains tend to develop smaller infarcts. CONCLUSION: The attenuated inflammatory response to stroke in aged animals may contribute to their smaller infarcts. The results presented here highlight the importance of using aged animals to investigate age-associated diseases like stroke, and should be considered as a major prerequisite in the development of age-adjusted therapeutic interventions.

  1. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  2. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex inter

  3. Analyzing inflammatory response as excitable media

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    Yde, Pernille; Høgh Jensen, Mogens; Trusina, Ala

    2011-11-01

    The regulatory system of the transcription factor NF-κB plays a great role in many cell functions, including inflammatory response. Interestingly, the NF-κB system is known to up-regulate production of its own triggering signal—namely, inflammatory cytokines such as TNF, IL-1, and IL-6. In this paper we investigate a previously presented model of the NF-κB, which includes both spatial effects and the positive feedback from cytokines. The model exhibits the properties of an excitable medium and has the ability to propagate waves of high cytokine concentration. These waves represent an optimal way of sending an inflammatory signal through the tissue as they create a chemotactic signal able to recruit neutrophils to the site of infection. The simple model displays three qualitatively different states; low stimuli leads to no or very little response. Intermediate stimuli leads to reoccurring waves of high cytokine concentration. Finally, high stimuli leads to a sustained high cytokine concentration, a scenario which is toxic for the tissue cells and corresponds to chronic inflammation. Due to the few variables of the simple model, we are able to perform a phase-space analysis leading to a detailed understanding of the functional form of the model and its limitations. The spatial effects of the model contribute to the robustness of the cytokine wave formation and propagation.

  4. Electronic cigarette exposure triggers neutrophil inflammatory responses.

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    Higham, Andrew; Rattray, Nicholas J W; Dewhurst, Jennifer A; Trivedi, Drupad K; Fowler, Stephen J; Goodacre, Royston; Singh, Dave

    2016-05-17

    The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP-9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry. ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens. ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use.

  5. Collective cell migration during inflammatory response

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    Wu, Di; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    Wound scratch healing assays of endothelial cell monolayers is a simple model to study collective cell migration as a function of biological signals. A signal of particular interest is the immune response, which after initial wounding in vivo causes the release of various inflammatory factors such as tumor necrosis alpha (TNF-α). TNF-α is an innate inflammatory cytokine that can induce cell growth, cell necrosis, and change cell morphology. We studied the effects of TNF-α on collective cell migration using the wound healing assays and measured several migration metrics, such as rate of scratch closure, velocities of leading edge and bulk cells, closure index, and velocity correlation functions between migrating cells. We observed that TNF-α alters all migratory metrics as a function of the size of the scratch and TNF-α content. The changes observed in migration correlate with actin reorganization upon TNF-α exposure.

  6. Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers.

    Science.gov (United States)

    Kox, Matthijs; Ramakers, Bart P; Pompe, Jan C; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W; Pickkers, Peter

    2011-08-01

    The autonomic nervous system and the inflammatory response are intimately linked. Heart rate variability (HRV) analysis is a widely used method to assess cardiac autonomic nervous system activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the acute inflammatory response to endotoxin. Second, we investigated whether the magnitude of the inflammatory response correlated with HRV alterations. Forty healthy volunteers received a single intravenous bolus of 2 ng/kg endotoxin (LPS, derived from Escherichia coli O:113). Of these, 12 healthy volunteers were administered LPS again 2 weeks later. Heart rate variability was determined at baseline (just before LPS administration) and hourly thereafter until 8 h after LPS administration. Plasma cytokine levels were determined at various time points. Baseline HRV indices did not correlate with the magnitude of the LPS-induced inflammatory response. Despite large alterations in HRV after LPS administration, the extent of the inflammatory response did not correlate with the magnitude of HRV changes. In subjects who were administered LPS twice, inflammatory cytokines were markedly attenuated after the second LPS administration, whereas LPS-induced HRV alterations were similar. Heart rate variability indices do not predict the acute inflammatory response in a standardized model of systemic inflammation. Although the acute inflammatory response results in HRV changes, no correlations with inflammatory cytokines were observed. Therefore, the magnitude of endotoxemia-related HRV changes does not reflect the extent of the inflammatory response.

  7. Platelets protect lung from injury induced by systemic inflammatory response

    Science.gov (United States)

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  8. Scorpion Venom and the Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Vera L. Petricevich

    2010-01-01

    Full Text Available Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability.

  9. A common assessment tool in inflammatory rheumatisms

    Directory of Open Access Journals (Sweden)

    Dan Nemeş

    2010-06-01

    Full Text Available Aims: Once the biologic therapies have been used, the present-day medicine trend is to homogenize the treatment of the inflammatory autoimmune rheumatic diseases, meaning rheumatoid arthritis (RA, ankylosing spondylitis (AS, psoriatic arthritis (PsA and systemic lupus erythematosus (SLE. But, there is still the need to find out a common assessment instrument for this pathology.Methods:The study included 120 patients (40 patients with RA, 40 patients with AS, 20 patients with PsA and 20 patients with SLE. They were assessed at the beginning and at the end of the study period by using both DAS (Disease Activity Score and HAQ (Health Assessment Questionnaire scales. BASDAI (Bath AS Disease Activity Index was used for AS patients and SLEDAI (SLE Disease Activity Index for SLE patients. Results: The RA patients had significant improvements regarding both DAS and HAQ scores (DAS mean score was initially 4.49 and finally 3.75; HAQ mean score was initially 1.78 and finally 2.15; p<0.05. Important improvements were registered in AS patients (DAS mean score was initially 5.25 and finally 4.02; HAQ mean score was initially 2.24 and finally 2.57; BASDAI mean score was initially 4.28 and finally 3.21; p<0.05, in PsA patients (DAS mean score was initially 7.32 and finally 5.15; HAQ mean score was initially 2.1 and finally 2.51; p<0.05 and in SLE patients (DAS mean score was initially 4.4 and finally 3.45; HAQ mean score was initially 1.9 and finally 2.4; SLEDAI mean score was initially 24.7 and finally 12.5; p<0.05.Conclusions:Having in view that the DAS scale analyses complex aspects (clinical activity of the disease, its inflammatory lab evidence, patient’s general health status, as well as its good correlation to other specific disease scales, it can be used as a more widely assessment instrument in the autoimmune inflammatory rheumatisms.

  10. [Therapeutic responsiveness in chronic inflammatory demyelinating polyradiculoneuropathy].

    Science.gov (United States)

    Iijima, Masahiro

    2011-11-01

    CIDP is autoimmune-associated peripheral neuropathy characterized by motor and sensory disturbances in each limb. While various phenotypes have been reported in CIDP, the essential pathogenesis is not elucidated yet. Clinicopathological study indicated axonal dysfunction (muscle atrophy and decreased compound muscular action potentials) is one of the most important factors in IVIg Non-responders. Furthermore, single nucleotide polymorphism (SNP) haplotype/diplotype analysis within a linkage disequilibrium block indicates transient axonal glycoprotein 1 (TAG-1), which controls proper distribution of potassium channels in juxtaparanode, is an important factor for IVIg responsiveness. Gene expression analysis of biopsied nerves supported the hypothesis that CIDP pathogenesis is involved in humoral and cellular immune system. With respect to IVIg responsiveness, expression profiles indicate whole CIDP patients need conventional immune-modulating therapies in somewhat, while we should re-consider how to use them. From aspects of gene expression results, Non-responders need not only conventional immune-modulating therapies but also other original modalities which could intervene the pathogenesis except Schwann/inflammatory cells while Responders with IVIg dependence should need stronger and longer immune-suppression.

  11. Inflammatory response after session of resistance exercises in untrained volunteers

    Directory of Open Access Journals (Sweden)

    Andre de Oliveira Teixeira

    2015-06-01

    Full Text Available The present study aimed to investigate the interaction between the blood cells, inflammatory markers, oxidative stress parameters and delayed onset muscle soreness (DOMS after a session of resistance exercise (SRE. The sample consisted of sixteen untrained men (26.4±5 years; 25.9±3 kg m-2. The SRE was composed of 4 sets of 10 repetitions maximum (extensor bench, squat and leg press for each exercise. Complete blood cell count, C-reactive protein (CRP, creatine kinase (CK, lipid peroxidation and antioxidant capacity against peroxyl radicals were previously evaluated (baseline, and at 0, 30 and 120 min. after the SRE. DOMS was assessed 24 hours after the exercises. Immediately after the SRE, an increase of blood cell number was observed; returning to baseline after 30 min. However, after 120 min., neutrophils showed higher values than the baseline and 30 min. assessments. CK and CRP increased progressively throughout the experiment. LPO increased immediately and 120 min. after the SRE. Untrained volunteers presented an apparent biphasic inflammatory response after an acute SRE and the changes in oxidative stress, inflammatory markers and leukocytosis were best evidenced two hours after exercise.

  12. Inflammatory Response to Nano- and Microstructured Hydroxyapatite

    Science.gov (United States)

    Mestres, Gemma; Espanol, Montserrat; Xia, Wei; Persson, Cecilia; Ginebra, Maria-Pau; Ott, Marjam Karlsson

    2015-01-01

    The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate’s microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials. PMID:25837264

  13. Inflammatory response to nano- and microstructured hydroxyapatite.

    Directory of Open Access Journals (Sweden)

    Gemma Mestres

    Full Text Available The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact and also in extracts i.e. media modified by the material (indirect contact. Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate's microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials.

  14. The influence of biomaterials on inflammatory responses to cardiopulmonary bypass.

    Science.gov (United States)

    Courtney, J M; Matata, B M; Yin, H Q; Esposito, A; Mahiout, A; Taggart, D P; Lowe, G D

    1996-05-01

    The nature of cardiopulmonary bypass and the complexity of the inflammatory response make the detection and interpretation of a biomaterial influence difficult. However, if mediation of the inflammatory response is considered to be an appropriate clinical goal, alteration to the biomaterial influence merits further investigation.

  15. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro;

    2011-01-01

    The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair.......The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair....

  16. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses

    OpenAIRE

    Laurence Madera; Anna Greenshields; Power Coombs, Melanie R.; Hoskin, David W.

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated...

  17. Action of Antiproteases on the Inflammatory Response in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Chun-Chia Chen

    2007-07-01

    Full Text Available The spectrum of acute pancreatitis ranges from mild edematous disease to a severe necrotizing process which is usually accompanied by local or systemic complications and even mortality. Early deaths (within the first week due to severe acute pancreatitis are generally caused by massive inflammatory responses which result in multiple organ failure. Although the exact mechanisms which trigger the inflammatory and necrotizing processes are not completely understood, it is generally accepted that autodigestion and activated leukocytes play important roles in the pathogenesis of acute pancreatitis. Proinflammatory cytokines are associated with systemic inflammatory response syndrome and multiple organ failure syndrome in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with systemic inflammatory response syndrome. Trypsin secreted by the pancreatic acinar cells activates proteaseactivated receptor-2 which can result in the production of cytokines. Protease inhibitors such as aprotinin, gabexate mesilate, nafamostat mesilate, ulinastatin, etc. can inhibit the various enzymes and inflammatory response in experimental and clinical studies. Thus, protease inhibitors have been considered as a potential treatment to inhibit the pancreatic inflammation in acute pancreatitis. The beneficial effects of antiproteases on experimental severe acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses. The effect of protease inhibitors on the inflammatory response in human acute pancreatitis deserves further study.

  18. Latent viral immune inflammatory response model for chronic multisymptom illness.

    Science.gov (United States)

    Maloney, Sean R; Jensen, Susan; Gil-Rivas, Virginia; Goolkasian, Paula

    2013-03-01

    A latent viral immune inflammatory response (LVIIR) model is presented which integrates factors that contribute to chronic multisymptom illness (CMI) in both the veteran and civilian populations. The LVIIR model for CMI results from an integration of clinical experience with a review of the literature in four distinct areas: (1) studies of idiopathic multisymptom illness in the veteran population including two decades of research on Gulf War I veterans with CMI, (2) new evidence supporting the existence of chronic inflammatory responses to latent viral antigens and the effect these responses may have on the nervous system, (3) recent discoveries concerning the role of vitamin D in maintaining normal innate and adaptive immunity including suppression of latent viruses and regulation of the immune inflammatory response, and (4) the detrimental effects of extreme chronic repetitive stress (ECRS) on the immune and nervous systems. The LVIIR model describes the pathophysiology of a pathway to CMI and presents a new direction for the clinical assessment of CMI that includes the use of neurological signs from a physical exam, objective laboratory data, and a new proposed latent viral antigen-antibody imaging technique for the peripheral and central nervous system. The LVIIR model predicts that CMI can be treated by a focus on reversal of immune system impairment, suppression of latent viruses and their antigens, and healing of nervous system tissue damaged by chronic inflammation associated with latent viral antigens and by ECRS. In addition, the LVIIR model suggests that maintaining optimal serum 25 OH vitamin D levels will maximize immune system suppression of latent viruses and their antigens and will minimize immune system inflammation. This model also emphasizes the importance of decreasing ECRS to improve immune system function and to minimize nervous system injury from excess serum glucocorticoid levels. The proposed model supports growing evidence that increasing

  19. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2014-01-01

    Full Text Available Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

  20. Effects of blood products on inflammatory response in endothelial cells in vitro.

    Directory of Open Access Journals (Sweden)

    Martin Urner

    Full Text Available BACKGROUND: Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. METHODS: The inflammatory response from pre-activated (endotoxin-stimulated and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC, platelet concentrates (PC and fresh frozen plasma (FFP was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. RESULTS: Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. CONCLUSION: Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.

  1. Airway inflammatory and atopy-related responses in athletes

    African Journals Online (AJOL)

    TAblE I. Studies on airway inflammatory responses to exercise. Author, year (ref) ... ples); post-exercise: unchanged after placebo or anti-inflammatory drugs. Boulet et al. 2005. 5 ... However, a recent study, using a canine model, demonstrated ...

  2. Pronounced inflammatory response to endotoxaemia during nighttime

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus; Lykkesfeldt, Jens

    2014-01-01

    endotoxaemia model. DESIGN AND METHODS: A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble...

  3. Pathophysiology of the systemic inflammatory response after major accidental trauma

    Directory of Open Access Journals (Sweden)

    Brøchner Anne

    2009-09-01

    Full Text Available Abstract Background The purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods An unsystematic review of the medical literature was performed and articles pertaining to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed. Trauma patients are, however, often exposed, not only to the trauma, but to several events in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated with increased risk of infection might develop. The inflammatory response is normalized 3 weeks following trauma. It has been proposed that the final reconstructive surgery should be postponed until the inflammatory response is normalized. This statement is however not based on clinical trials. Conclusion Postponement of final reconstructive surgery until the inflammatory is normalized should be based on prospective randomized trials.

  4. Pathophysiology of the systemic inflammatory response after major accidental trauma.

    Science.gov (United States)

    Brøchner, Anne Craveiro; Toft, Palle

    2009-09-15

    The purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. An unsystematic review of the medical literature was performed and articles pertaining to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed. Trauma patients are, however, often exposed, not only to the trauma, but to several events in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated with increased risk of infection might develop. The inflammatory response is normalized 3 weeks following trauma. It has been proposed that the final reconstructive surgery should be postponed until the inflammatory response is normalized. This statement is however not based on clinical trials. Postponement of final reconstructive surgery until the inflammatory is normalized should be based on prospective randomized trials.

  5. Infection with Mycobacterium ulcerans Induces Persistent Inflammatory Responses in Mice

    Science.gov (United States)

    Oliveira, Martinha S.; Fraga, Alexandra G.; Torrado, Egídio; Castro, António G.; Pereira, João P.; Filho, Adhemar Longatto; Milanezi, Fernanda; Schmitt, Fernando C.; Meyers, Wayne M.; Portaels, Françoise; Silva, Manuel T.; Pedrosa, Jorge

    2005-01-01

    Buruli ulcer (BU) is a devastating, necrotizing, tropical skin disease caused by infections with Mycobacterium ulcerans. In contrast to other mycobacterioses, BU has been associated with minimal or absent inflammation. However, here we show that in the mouse M. ulcerans induces persistent inflammatory responses with virulence-dependent patterns. Mycolactone-positive, cytotoxic strains are virulent for mice and multiply progressively, inducing both early and persistent acute inflammatory responses. The cytotoxicity of these strains leads to progressive destruction of the inflammatory infiltrates by postapoptotic secondary necrosis, generating necrotic acellular areas with extracellular bacilli released by the lysis of infected phagocytes. The necrotic areas, always surrounded by acute inflammatory infiltrates, expand through the progressive invasion of healthy tissues around the initial necrotic lesions by bacteria and by newly recruited acute inflammatory cells. Our observations show that the lack of inflammatory infiltrates in the extensive areas of necrosis seen in advanced infections results from the destruction of continuously produced inflammatory infiltrates and not from M. ulcerans-induced local or systemic immunosuppression. Whether this is the mechanism behind the predominance of minimal or absent inflammatory responses in BU biopsies remains to be elucidated. PMID:16177301

  6. Systemic inflammatory responses following welding inhalation challenge test

    Directory of Open Access Journals (Sweden)

    Paula Kauppi

    2015-01-01

    Conclusions: Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

  7. Platelets as Central Mediators of Systemic Inflammatory Responses

    OpenAIRE

    Smith, Tammy L; Weyrich, Andrew S.

    2010-01-01

    Systemic inflammatory responses are associated with high morbidity and mortality and represent a diverse and clinically challenging group of diseases. Platelets are increasingly linked to inflammation, in addition to their well-known roles in hemostasis and thrombosis. There is agreement that traditional functions of platelets, including adherence, aggregation, and secretion of preformed mediators, contribute to systemic inflammatory responses. However, emerging evidence indicates that platel...

  8. Macrophage Expression of Inflammatory Genes in Response to EMCV Infection

    Directory of Open Access Journals (Sweden)

    Zachary R. Shaheen

    2015-08-01

    Full Text Available The expression and production of type 1 interferon is the classic cellular response to virus infection. In addition to this antiviral response, virus infection also stimulates the production of proinflammatory mediators. In this review, the pathways controlling the induction of inflammatory genes and the roles that these inflammatory mediators contribute to host defense against viral pathogens will be discussed. Specific focus will be on the role of the chemokine receptor CCR5, as a signaling receptor controlling the activation of pathways leading to virus-induced inflammatory gene expression.

  9. Fetal inflammatory response and brain injury in the preterm newborn.

    Science.gov (United States)

    Malaeb, Shadi; Dammann, Olaf

    2009-09-01

    Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

  10. Inflammatory responses to Hydroxyapatite implants in middle ear in rats

    Institute of Scientific and Technical Information of China (English)

    YE Qing; JIANG Yi; WANG Xiao-yan; ZHENG Ke-fei

    2008-01-01

    Objective To study local inflammatory response after implantation of hydroxyapatite synthetic ossicular prosthesis. Methods Hydroxyapatite gantries were implanted in the bulla in 32 rats. Sham surgical procedures were performed in 10 rats as the control. Animals were sacrificed at 1 to 300 days after surgery. Bulla sections, stained with HE and Mallory's azan, were examined for numbers and percentages of various inflammatory cell types. Results Slightly more inflammatory reaction was seen in animals with the implant than in the controls, mostly during the early stage following the implantation procedure. Few inflammatory cells were observed at later times. There were satisfactory fibrosis in both implanted and control ears. Conclusion The results indicate that hydroxyapatite synthetic prosthesis is a biocompatible implantation material in the middle ear. Nonetheless, the presence of inflammatory reaction immediately following implantation implies that control of infection is important in the early times after the implantation procedure.

  11. Messengers without borders: mediators of systemic inflammatory response in AKI.

    Science.gov (United States)

    Ratliff, Brian B; Rabadi, May M; Vasko, Radovan; Yasuda, Kaoru; Goligorsky, Michael S

    2013-03-01

    The list of signals sent by an injured organ to systemic circulation, so-called danger signals, is growing to include multiple metabolites and secreted moieties, thus revealing a highly complex and integrated network of interlinked systemic proinflammatory and proregenerative messages. Emerging new data indicate that, apart from the well established local inflammatory response to AKI, danger signaling unleashes a cascade of precisely timed, interdependent, and intensity-gradated mediators responsible for development of the systemic inflammatory response. This fledgling realization of the importance of the systemic inflammatory response to the localized injury and inflammation is at the core of this brief overview. It has a potential to explain the additive effects of concomitant diseases or preexisting chronic conditions that can prime the systemic inflammatory response and exacerbate it out of proportion to the actual degree of acute kidney damage. Although therapies for ameliorating AKI per se remain limited, a potentially powerful strategy that could reap significant benefits in the future is to modulate the intensity of danger signals and consequently the systemic inflammatory response, while preserving its intrinsic proregenerative stimuli.

  12. Translation Control: A Multifaceted Regulator of Inflammatory Response

    Science.gov (United States)

    Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

    2010-01-01

    A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832

  13. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

    Science.gov (United States)

    Borovikova, Lyudmila V.; Ivanova, Svetlana; Zhang, Minghuang; Yang, Huan; Botchkina, Galina I.; Watkins, Linda R.; Wang, Haichao; Abumrad, Naji; Eaton, John W.; Tracey, Kevin J.

    2000-05-01

    Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

  14. Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen.

    Directory of Open Access Journals (Sweden)

    Shankar J Evani

    Full Text Available Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation.

  15. Pathophysiology of the systemic inflammatory response after major accidental trauma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Toft, Palle

    2009-01-01

    ABSTRACT: BACKGROUND: Purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods: An unsystematic review of the medical literature was performed and articles pertaining to the in......ABSTRACT: BACKGROUND: Purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods: An unsystematic review of the medical literature was performed and articles pertaining...... to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion: The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma...... and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed.Trauma patients are, however, often exposed, not only to the trauma, but to several evens in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated...

  16. Saturated fatty acids trigger TLR4-mediated inflammatory response.

    Science.gov (United States)

    Rocha, D M; Caldas, A P; Oliveira, L L; Bressan, J; Hermsdorff, H H

    2016-01-01

    Toll-like receptors (TLR) mediate infection-induced inflammation and sterile inflammation by endogenous molecules. Among the TLR family, TLR4 is the best understood. However, while its downstream signaling pathways have been well defined, not all ligands of TLR4 are currently known. Current evidence suggests that saturated fatty acids (SFA) act as non-microbial TLR4 agonists, and trigger its inflammatory response. Thus, our present review provides a new perspective on the potential mechanism by which SFAs could modulate TLR4-induced inflammatory responses: (1) SFAs can be recognized by CD14-TLR4-MD2 complex and trigger inflammatory pathways, similar to lipopolysaccharide (LPS). (2) SFAs lead to modification of gut microbiota with an overproduction of LPS after a high-fat intake, enhancing this natural TLR4 ligand. (3) In addition, this metabolic endotoxemia leads to an oxidative stress thereby producing atherogenic lipids - oxLDL and oxidized phospholipids - which trigger CD36-TLR4-TLR6 inflammatory response. (4) Also, the high SFA consumption increases the lipemia and the mmLDL and oxLDL formation through oxidative modifications of LDL. The mmLDL, unlike oxLDL, is involved in activation of the CD14-TLR4-MD2 inflammatory pathway. Those molecules can induce TLR4 inflammatory response by MyD88-dependent and/or MyD88-independent pathways that, in turn, promotes the expression of proinflammatory transcript factors such as factor nuclear kappa B (NF-κB), which plays a crucial role in the induction of inflammatory mediators (cytokines, chemokines, or costimulatory molecules) implicated in the development and progression of many chronic diseases.

  17. Suppression of inflammatory responses by labdane-type diterpenoids.

    Science.gov (United States)

    Girón, Natalia; Través, Paqui G; Rodríguez, Benjamín; López-Fontal, Raquel; Boscá, Lisardo; Hortelano, Sonsoles; de las Heras, Beatriz

    2008-04-15

    A series of 11 labdane-type diterpenoids (1-11) with various patterns of substitution were tested for potential anti-inflammatory activity. Of these compounds, 4 and 11 were selected to evaluate their influence on targets relevant to the regulation of the inflammatory response. These diterpenoids reduced the production of nitric oxide (NO), prostaglandin E2, and tumor necrosis factor-alpha in LPS-activated RAW 264.7 macrophages, with IC50 in the range 1-10 microM. Inhibition of these inflammatory mediators was related to inhibition of the expression of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) at the transcriptional level, as determined by western-blot and RT-PCR. Examination of the effects of these diterpenoids on nuclear factor kappaB signaling showed that both compounds inhibit the phosphorylation of IkappaBalpha and IkappaBbeta, preventing their degradation and the nuclear translocation of the NF-kappaB p65 subunit. Inhibition of IKK activity was also observed. These derivatives displayed significant anti-inflammatory activity in vivo, suppressing mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibiting myeloperoxidase activity, an index of neutrophil infiltration. The anti-inflammatory effects of these labdane diterpenoids, together with their low cell toxicity, suggest potential therapeutic applications in the regulation of the inflammatory response.

  18. Inflammatory biomarkers in saliva: assessing the strength of association of diabetes mellitus and periodontal status with the oral inflammatory burden.

    Science.gov (United States)

    Yoon, Angela J; Cheng, Bin; Philipone, Elizabeth; Turner, Ryan; Lamster, Ira B

    2012-05-01

    To determine the strength of association of type 2 diabetes mellitus and periodontal disease with the oral inflammatory burden, as assessed by markers of inflammation in saliva. Unstimulated saliva samples were collected from 192 subjects with or without type 2 diabetes. β-glucuronidase (βG) was measured via a fluorometric array and interlukin-1β (IL-1β) via enzyme-linked immunosorbent assay. The concentration of both mediators was evaluated in relationship to clinical parameters, severity of periodontal disease and diabetes status. Regression analysis demonstrated that diabetes and periodontal disease was independently and positively correlated with increased concentration of βG in saliva (p periodontal disease with the level of βG in saliva was greater than the strength of association of the diabetic status. IL-1β concentration in saliva was primarily associated with the severity of periodontal disease (p diabetes (p = 0.50). This study examined the nature of the inflammatory response in the oral cavity as assessed by inflammatory markers in saliva. Both periodontal disease and diabetes mellitus were independently associated with the oral inflammatory burden, in which the effect of periodontal disease was more pronounced. © 2012 John Wiley & Sons A/S.

  19. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  20. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  1. Syk-Mediated Suppression of Inflammatory Responses by Cordyceps bassiana.

    Science.gov (United States)

    Yang, Woo Seok; Nam, Gyeong Sug; Kim, Mi-Yeon; Cho, Jae Youl

    2017-01-01

    The fruit body of artificially cultivated Cordyceps bassiana has been reported to exhibit anti-inflammatory and anticancer activities. Although it has been suggested that the fruit body has neutraceutic and pharmaceutic biomaterial potential, the exact anti-inflammatory molecular mechanism has not been fully elucidated. In this study, we demonstrated the immunopharmacologic activity of Cordyceps bassiana under in vitro conditions and investigated its anti-inflammatory mechanism. Water extract (Cm-WE) of the fruit body of artificially cultivated Cordyceps bassiana without polysaccharide fractions reduced the expression of the proinflammatory genes cyclooxygenase (COX)-2, interleukin (IL)-12, and inducible nitric oxide synthase (iNOS) and promoted the expression of the anti-inflammatory gene IL-10 in lipopolysaccharide (LPS)-treated RAW264.7 cells. In addition, this fraction suppressed proliferation and interferon (IFN)-[Formula: see text] production in splenic T lymphocytes. Cm-WE blocked the activation of nuclear factor (NF)-[Formula: see text]B and activator protein (AP)-1 and their upstream inflammatory signaling cascades, including Syk, MEK, and JNK. Using kinase assays, Syk was identified as the target enzyme most strongly inhibited by Cm-WE. These results strongly suggest that Cm-WE suppresses inflammatory responses by inhibiting Syk kinase activity, with potential implications for novel neutraceutic and pharmaceutic biomaterials.

  2. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro;

    2011-01-01

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...

  3. COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

    Science.gov (United States)

    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  4. Factors modulating the inflammatory response in acute gouty arthritis

    NARCIS (Netherlands)

    Cleophas, M.C.P.; Crisan, T.O.; Joosten, L.A.B.

    2017-01-01

    PURPOSE OF REVIEW: Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric

  5. The Pathogenesis of ACLF: The Inflammatory Response and Immune Function.

    Science.gov (United States)

    Moreau, Richard

    2016-05-01

    Although systemic inflammation is a hallmark of acute-on-chronic liver failure (ACLF), its role in the development of this syndrome is poorly understood. Here the author first summarizes the general principles of the inflammatory response. Inflammation can be triggered by exogenous or endogenous inducers. Important exogenous inducers include bacterial products such as pathogen-associated molecular patterns (PAMPs) and virulence factors. Pathogen-associated molecular patterns elicit inflammation through structural feature recognition (using innate pattern-recognition receptors [PRRs]), whereas virulence factors generally trigger inflammation via functional feature recognition. Endogenous inducers are called danger-associated molecular patterns (DAMPs) and include molecules released by necrotic cells and products of extracellular matrix breakdown. Danger-associated molecular patterns use different PRRs. The purpose of the inflammatory response may differ according to the type of stimulus: The aim of infection-induced inflammation is to decrease pathogen burden, whereas the DAMP-induced inflammation aims to promote tissue repair. An excessive inflammatory response can induce collateral tissue damage (a process called immunopathology). However immunopathology may not be the only mechanism of tissue damage; for example, organ failure can develop because of failed disease tolerance. In this review, the author also discusses how general principles of the inflammatory response can help us to understand the development of ACLF in different contexts: bacterial infection, severe alcoholic hepatitis, and cases in which there is no identifiable trigger.

  6. Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Woodward, Elizabeth; Bojesen, Anders Miki

    2012-01-01

    The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-a, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine...... inoculation of 105 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality...

  7. Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions.

    Science.gov (United States)

    Nonaka, Fumiaki; Migita, Kiyoshi; Haramura, Tomoko; Sumiyoshi, Remi; Kawakami, Atsushi; Eguchi, Katsumi

    2014-05-01

    Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

  8. Risk factors for systemic inflammatory response after congenital cardiac surgery.

    Science.gov (United States)

    Güvener, Murat; Korun, Oktay; Demirtürk, Orhan Saim

    2015-01-01

    This study aims to assess the frequency of systemic inflammatory response syndrome (SIRS) following congenital heart surgery and risk factors associated with this clinical syndrome. Charts of all patients undergoing surgery for congenital heart disease in a single institution over a five-year period were analyzed retrospectively. The presence of SIRS was evaluated based on the criteria of the International Pediatric Sepsis Consensus Conference. Of the 246 patients included in the study 22 (8.9%) had clinical parameters indicating SIRS. The patients in the SIRS group had significantly longer cardiopulmonary bypass time (105.14 ± 27.27 vs. 66.86 ± 26.64 min; p SIRS group. Binary logistic regression revealed cardiopulmonary bypass time (OR: 1.05, p SIRS. SIRS was also found to be a strong independent predictor of mortality (OR: 10.13, p SIRS after congenital heart surgery is associated with increased mortality. Independent risk factors for SIRS in the patient population of the study were cardiopulmonary bypass time, body weight below 10 kg and preoperative diagnosis of right to left shunt congenital heart disease. © 2014 Wiley Periodicals, Inc.

  9. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Science.gov (United States)

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  10. Non Inflammatory Boronate Based Glucose-Responsive Insulin Delivery Systems

    Science.gov (United States)

    Dasgupta, Indrani; Tanifum, Eric A.; Srivastava, Mayank; Phatak, Sharangdhar S.; Cavasotto, Claudio N.; Analoui, Mostafa; Annapragada, Ananth

    2012-01-01

    Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L–40 mmoles/L). The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger. PMID:22272238

  11. DMPD: Cytokine signaling modules in inflammatory responses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18400190 Cytokine signaling modules in inflammatory responses. O'Shea JJ, Murray PJ...tory responses. PubmedID 18400190 Title Cytokine signaling modules in inflammatory responses. Authors O'Shea JJ, Murray

  12. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.

    Science.gov (United States)

    Vieira, Mônica L.; Naudin, Clément; Mörgelin, Matthias; Romero, Eliete C.; Nascimento, Ana Lucia T. O.; Herwald, Heiko

    2016-01-01

    Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. In severe infections, hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. In the present investigation, we aimed to analyze the modulation of the hemostatic and inflammatory host responses by the bacterial pathogen Leptospira. The effects of leptospires and their secreted products on stimulation of human intrinsic and extrinsic pathways of coagulation were investigated by means of altered clotting times, assembly and activation of contact system and induction of tissue factor. We show that both extrinsic and intrinsic coagulation cascades are modulated in response to Leptospira or leptospiral secreted proteins. We further find that the pro-inflammatory mediator bradykinin is released following contact activation at the bacterial surface and that pro-coagulant microvesicles are shed from monocytes in response to infection. Also, we show that human leptospirosis patients present higher levels of circulating pro-coagulant microvesicles than healthy individuals. Here we show that both pathways of the coagulation system are modulated by leptospires, possibly leading to altered hemostatic and inflammatory responses during the disease. Our results contribute to the understanding of the leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments for the severe manifestations of the disease. PMID:27167223

  13. Innate immune response to pulmonary contusion: Identification of cell-type specific inflammatory responses

    OpenAIRE

    Hoth, J. Jason; Wells, Jonathan D.; Yoza, Barbara K.; McCall, Charles E.

    2012-01-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll like receptors 2 and 4 (TLR2 and TLR4) mediate the ...

  14. Systemic inflammatory response syndrome (SIRS): where did it come from and is it still relevant today?

    Science.gov (United States)

    Balk, Robert A

    2014-01-01

    The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition.

  15. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    OpenAIRE

    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants). Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: "inflammatory bowel disease (IBD)" OR "Crohn′s dise...

  16. The inflammatory response to vaccination is altered in the elderly.

    Science.gov (United States)

    El Yousfi, Mimoun; Mercier, Sabine; Breuillé, Denis; Denis, Philippe; Papet, Isabelle; Mirand, Philippe Patureau; Obled, Christiane

    2005-08-01

    To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and acute phase proteins were analysed before and 2 days after vaccination. Prior to vaccination, only IFN-gamma production was lower in the elderly than in the young subjects due to a lower mononuclear cell number. In the same time, although in the normal range, several acute phase proteins were greater in elderly than in young subjects, suggesting a low-grade inflammatory state in the elderly. After vaccination, IFN-gamma production remained lower in the elderly than in the young, supporting an altered cell-mediated immunity with advancing age. TNF-alpha production was unaffected by either ageing or vaccination. IL-6 production was stimulated by vaccination in young subjects but not significantly in the elderly. IL-10 production was inhibited by vaccination in the elderly but not in the young. Acute phase proteins were less increased in elderly than in young subjects. Taken together, these results support a general lack of inflammatory response in the elderly exposed to an immune challenge and suggest that immune deficiency may concern both Th1 and Th2 responses. However, the interpretation must respect the limitation of small subjects number.

  17. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Science.gov (United States)

    Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

  18. The role of tissue factor in systemic inflammatory response syndrome.

    Science.gov (United States)

    Egorina, Elena M; Sovershaev, Mikhail A; Hansen, John-Bjarne

    2011-09-01

    Tissue factor (TF) is a major initiator of extrinsic pathway of blood coagulation. A dual role of TF in the extensive crosstalk between blood coagulation and inflammation has recently become apparent. The majority of the cases of systemic inflammatory response syndrome, disseminated intravascular coagulation, and sepsis are accompanied by hyperactivation of TF in circulating monocytes and damaged tissue. Systemic Gram-negative infection induces expression of TF by vascular cells. In addition to extrinsic coagulation pathway, TF induces proinflammatory signaling cascade originating from activation of protease-activated receptors. Because TF-activated proteolytic cascade is placed in a nexus between coagulation and inflammation, early modulation of TF activity presently becomes a tempting experimental therapeutic strategy in systemic inflammatory response syndrome patients.

  19. Inflammatory Responses to Salmonella Infections Are Serotype-Specific

    Directory of Open Access Journals (Sweden)

    Zhanna Ktsoyan

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the profile of inflammatory response in patients with acute salmonellosis caused by two serotypes of Salmonella enterica, S. Enteritidis and S. Typhimurium, as well as in convalescent patients with previous acute disease caused by S. Enteritidis. Patients with acute disease showed significantly elevated levels of IL-1β, IL-17, IL-10, and calprotectin compared to healthy control subjects. In convalescent patients, these markers were also significantly elevated, with the exception of IL-1β. Multivariate statistical analyses with the use of these variables produced models with a good predictive accuracy resulting in excellent separation of the diseased and healthy cohorts studied. Overall, the results suggest that the profile of inflammatory response in this disease is determined, to a significant degree, by the serotype of Salmonella, and the profile of certain cytokines and calprotectin remains abnormal for a number of months following the acute disease stage.

  20. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  1. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells

    Science.gov (United States)

    Palmieri, Erika M.; Menga, Alessio; Lebrun, Aurore; Hooper, Douglas C.; Butterfield, D. Allan

    2017-01-01

    Abstract Aims: Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. Results: GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Innovation: Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Conclusions: Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351–363. PMID:27758118

  2. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

    OpenAIRE

    2014-01-01

    The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an...

  3. Inflammatory and bone remodeling responses to the cytolethal distending toxins

    OpenAIRE

    2014-01-01

    The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an e...

  4. Inflammatory and Immune Responses to Surgery and Their Clinical Impact.

    Science.gov (United States)

    Alazawi, William; Pirmadjid, Negar; Lahiri, Rajiv; Bhattacharya, Satyajit

    2016-07-01

    The aim of this study was to describe current understanding of the local and systemic immune responses to surgery and their impact on clinical outcomes, predictive biomarkers, and potential treatment strategies. Patients undergoing major surgery are at risk of life-threatening inflammatory complications that include infection, the systemic inflammatory response syndrome (SIRS), or sepsis. Although improvements in surgical technique and peri-operative care have resulted in reduction in the rates of these complications, they remain high, especially in patients undergoing complex abdominal procedures. There are currently no drugs licensed specifically for the treatment of sepsis nor is it possible to identify those at highest risk, which would allow pre-emptive therapy that may improve outcomes. Local immune responses to surgery lead to systemic pro-inflammatory and immunosuppressive phases that are temporally related and proportionate in magnitude. Improved understanding of these mechanisms has implications for clinical study design and has led to the emergence of novel biomarkers such as Toll-like receptor expression. These can be used to stratify patient care pathways to maximize the benefit from current therapies or to select the right target at the right phase of illness for future drug development.

  5. Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection

    Directory of Open Access Journals (Sweden)

    Caroline eBlackwell

    2015-03-01

    Full Text Available The risk factors for Sudden Infant Death Syndrome (SIDS parallel those associated with susceptibility to or severity of infectious diseases. There is no evidence that a single infectious agent is associated with SIDS; the common thread appears to be induction of inflammatory responses to infections. In this review, interactions between genetic and environmental risk factors for SIDS are assessed in relation to the hypothesis that many infant deaths result from dysregulation of inflammatory responses to minor infections. Risk factors are assessed in relation to three important stages of infection: 1 bacterial colonisation (frequency or density; 2 induction of temperature-dependent toxins; 3 induction or control of inflammatory responses.In this article we review the interactions among risk factors for SIDS for their effects on induction or control of inflammatory responses. The risk factors studied are genetic factors (sex, cytokine gene polymorphisms among ethnic groups at high or low risk of SID; developmental stage (changes in cortisol and testosterone levels associated with 2-4 month age range; environmental factors (virus infection, exposure to cigarette smoke. These interactions help to explain differences in the incidences of SIDS observed between ethnic groups prior to public health campaigns to reduce these infant deaths.

  6. The cellular inflammatory response in human spinal cords after injury.

    Science.gov (United States)

    Fleming, Jennifer C; Norenberg, Michael D; Ramsay, David A; Dekaban, Gregory A; Marcillo, Alexander E; Saenz, Alvaro D; Pasquale-Styles, Melissa; Dietrich, W Dalton; Weaver, Lynne C

    2006-12-01

    Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative

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

    Directory of Open Access Journals (Sweden)

    Aja M Rieger

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

  8. Protective value of piroxicam on the enhanced inflammatory response after whole body irradiation

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    el-Ghazaly, M.; Saleh, S.; Kenawy, S.; Roushdy, H.M.; Khayyal, M.T.

    1986-06-01

    The anti-inflammatory activity of piroxicam was assessed after whole body irradiation in rats. Two models of inflammation, the carrageenan-induced edema and the adjuvant-induced arthritis in rats have been utilised. Piroxicam at doses of 1, 5 and 10 mg kg-1 i.p. was effective in inhibiting the paw edema produced in both models of inflammation. The inflammatory response in irradiated was significantly higher than that produced in normal animals and was dependent on the radiation dose level used (0.5-2 Gy). The effect of piroxicam on the late inflammatory response produced by exposure to 2 Gy was studied by measuring the carrageenan-induced edema 4 h after irradiation and on the third and seventh day thereafter. The increase in paw volume was significantly suppressed in animals receiving the drug. Administration of piroxicam (5 mg kg-1) one hour before irradiation of animals at 0.5 Gy, produced inhibition to the exaggerated inflammatory response in irradiated animals. This suggests that piroxicam possibly owes its protective value to prevention of the increase in cellular permeability induced by radiation. Alternatively, the drug may exert this effect by inhibiting PG synthesis, thereby reducing their potentiating influence on the other mediators of inflammation. Furthermore, the inhibition of lysosomal enzyme release possibly induced by the drug may contribute to the probable reduction in the release of inflammatory mediators.

  9. Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

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    Kenji Hashimoto

    2015-04-01

    Full Text Available Although antidepressants are generally effective in the treatment of major depressive disorder (MDD, it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA receptor antagonist ketamine.

  10. Systemic inflammatory responses during laparoscopic and open inguinal hernia repair: a randomised prospective study

    DEFF Research Database (Denmark)

    Jess, P; Schultz, Karen; Bendtzen, K

    2000-01-01

    To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed.......To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed....

  11. The Inflammatory Response in Psoriasis: a Comprehensive Review.

    Science.gov (United States)

    Deng, Yaxiong; Chang, Christopher; Lu, Qianjin

    2016-06-01

    Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis. The interplay of immune cells and cytokines is another critical factor in the pathogenesis of psoriasis. These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to its pro-inflammatory effects and its involvement in an integrated inflammatory loop with dendritic cells and keratinocytes, contributing to an overproduction of antimicrobial peptides, inflammatory cytokines, and chemokines that leads to amplification of the immune response. In addition, other pathways and signaling molecules have been found to be involved, including Th9, Th22, regulatory T cells, γδ T cells, CD8(+) T cells, and their related cytokines. Understanding the pathogenesis of psoriasis will allow us to develop increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules. There is no cure for psoriasis at the present time, and much of the treatment involves managing the symptoms. The biologics, while lacking the adverse effects associated with some of the traditional medications such as corticosteroids and methotrexate, have their own set of side effects, which may include reactivation of latent infections. Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis.

  12. Inflammatory responses in the rat superior colliculus after eye enucleation.

    Science.gov (United States)

    Hernandes, Marina S; Britto, Luiz R G

    2014-02-01

    Ocular enucleation induces profound morphological alterations in central visual areas. However, little is known about the response of glial cells and possible inflammatory processes in visual brain areas resulting from eye enucleation. In this study, immunoblotting and immunostaining assays revealed increased expression of astrocyte and microglia markers in the rat superior colliculus (SC) between 1 and 15 days after contralateral enucleation. A transient increase of neuronal COX-2 protein expression was also found in the SC. To evaluate the role of an anti-inflammatory drug in attenuating both COX-2 and glial cell activation, the synthetic glucocorticoid dexamethasone (DEX) was administered (1 mg/kg i.p., for 3 days) to enucleated rats. Immunoblotting data revealed that DEX treatment significantly inhibited COX-2 protein expression. Postlesion immunostaining for astrocyte and microglia markers was also significantly reduced by DEX treatment. These findings suggest that the removal of retinal ganglion cell input generates inflammatory responses in central retinorecipient structures. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Inflammatory response to strenuous muscular exercise in man

    Directory of Open Access Journals (Sweden)

    G. Camus

    1993-01-01

    Full Text Available Based on the humoral and cellular changes occurring during strenuous muscular work in humans, the concept of inflammatory response to exercise (IRE is developed. The main indices of IRE consist of signs of an acute phase response, leucocytosis and leucocyte activation, release of inflammatory mediators, tissue damage and cellular infiltrates, production of free radicals, activation of complement, and coagulation and fibrinolytic pathways. Depending on exercise intensity and duration, it seems likely that muscle and/or associated connective tissue damage, contact system activation due to shear stress on endothelium and endotoxaemia could be the triggering mechanisms of IRE. Although this phenomenon can be considered in most cases as a physiological process associated with tissue repair, exaggerated IRE could have physiopathological consequences. On the other hand, the influence of several factors such as age, sex, training, hormonal status, nutrition, anti-inflammatory drugs, and the extent to which IRE could be a potential risk for subjects undergoing intense physical training require further study.

  14. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants

    Science.gov (United States)

    de Andrade, Camila Alves; Oliveira, Katherine Simone Caires; Tossige-Gomes, Rosalina; Rocha-Vieira, Etel; Neves, Camila Danielle Cunha; Vieira, Érica Leandro Marciano; Leite, Hércules Ribeiro; Oliveira, Murilo Xavier; Júnior, Antônio Lúcio Teixeira; Coimbra, Cândido Celso

    2016-01-01

    Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF) and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group) between 6 and 24 months. Plasma levels of leptin, adiponectin, resistin, soluble tumor necrosis factor (TNF) receptors, chemokines, BDNF, serum cortisol and redox status were measured. Unpaired Student's t-test was used to analyze the results and a probability of p<0.05 was acceptable for rejection of the null hypothesis. The Pearson correlation was used to verify the association between the biomarkers analyzed in each group. Plasma levels of leptin (p = 0.0001), adiponectin (p = 0.0007) and BDNF (p = 0.003), and serum cortisol (p = 0.048) were significantly higher in overweight/obese infants than normal-weight infants. In contrast, the concentration of thiobarbituric acid reactive substances (TBARS) (p = 0.004), and catalase (p = 0.045) and superoxide dismutase activity (p = 0.02) were lower in overweight/obese infants than normal-weight peers. All the results together indicate neuroendocrine inflammatory response changes in overweight/obese infants between 6 and 24 months. Although there is already an environment that predisposes for a subsequent pro-inflammatory response, neuroendocrine secretion changes that permit the control of the inflammatory process in this age interval can be observed. PMID:27907172

  15. Targeting the inflammatory response in healing myocardial infarcts.

    Science.gov (United States)

    Frangogiannis, Nikolaos G

    2006-01-01

    Healing of myocardial infarcts depends on an inflammatory cascade that ultimately results in clearance of dead cells and matrix debris and formation of a scar. Myocardial necrosis activates complement, Nuclear Factor (NF)-kappaB and Toll-like Receptor (TLR)-dependent pathways, and generates free radicals, triggering an inflammatory response. Chemokines and cytokines are markedly induced in the infarct and mediate recruitment and activation of neutrophils and mononuclear cells. Extravasation of platelets and plasma proteins, such as fibrinogen and fibronectin, results in formation of a clot, consisting of platelets embedded in a mesh of crosslinked fibrin. This provisional matrix provides a scaffold for migration of cells into the infarct. Monocytes differentiate into macrophages and secrete fibrogenic and angiogenic growth factors inducing formation of granulation tissue, containing myofibroblasts and neovessels. Repression of proinflammatory cytokine and chemokine synthesis, mediated in part through Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10, is critical for resolution of the inflammatory infiltrate and transition to fibrous tissue deposition. Infarct myofibroblasts deposit extracellular matrix proteins and a collagen-based scar is formed. As the wound matures, fibroblasts undergo apoptosis and neovessels regress, resulting in formation of a scar with a low cellular content containing dense, cross-linked collagen. The pathologic and structural changes associated with infarct healing directly influence ventricular remodeling and affect prognosis in patients with myocardial infarction. Understanding the mechanisms involved in the regulation of the post-infarction inflammatory response, and the spatial and temporal parameters of wound healing is necessary in order to identify specific molecular targets for therapeutic intervention.

  16. Dimethyl sulfoxide (DMSO) attenuates the inflammatory response in the in vitro intestinal Caco-2 cell model.

    Science.gov (United States)

    Hollebeeck, Sylvie; Raas, Thomas; Piront, Neil; Schneider, Yves-Jacques; Toussaint, Olivier; Larondelle, Yvan; During, Alexandrine

    2011-10-30

    This study aimed to investigate dose effects of dimethyl sulfoxide (DMSO) (0.05-1%) on the intestinal inflammatory response in confluent- and differentiated-Caco-2 cells stimulated with interleukin (IL)-1β or a pro-inflammatory cocktail for 24 h. Cyclooxygenase-2 (COX-2) activity was assayed by incubating inflamed cells with arachidonic acid and then measuring prostaglandin-E(2) (PGE(2)) produced. Soluble mediators (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and COX-2-derived PGE(2)) were quantified by enzyme immunoassays and mRNA expression of 33 proteins by high throughput TaqMan Low Density Array. Data showed that DMSO decreased induced IL-6 and MCP-1 secretions in a dose-dependent manner (PDMSO dose-dependently reduced COX-2-derived PGE(2) (PDMSO at 0.5% decreased significantly mRNA levels of 14 proteins involved in the inflammatory response (including IL-6, IL-1α, IL-1β, and COX-2). Thus, DMSO at low concentrations (0.1-0.5%) exhibits anti-inflammatory properties in the in vitro intestinal Caco-2 cell model. This point is important to be taken into account when assessing anti-inflammatory properties of bioactive compounds requiring DMSO as vehicle, such as phenolic compounds, in order to avoid miss-interpretation of the results. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Directory of Open Access Journals (Sweden)

    Iva Bozic

    Full Text Available Microglial cells are resident immune cells of the central nervous system (CNS, recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS and NO; cyclooxygenase-2 (COX-2, heat-shock protein 70 (Hsp70, tumor necrosis factor alpha α (TNF-α, interleukin-6 (IL-6, whereas it increased anti-inflammatory interleukin-10 (IL-10 production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2, c-Jun N-terminal kinases (JNK and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB in the nucleus. Therefore

  18. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  19. The Transcriptome of the Fetal Inflammatory Response Syndrome

    Science.gov (United States)

    Madsen-Bouterse, Sally A.; Romero, Roberto; Tarca, Adi L.; Kusanovic, Juan Pedro.; Espinoza, Jimmy; Kim, Chong Jai; Kim, Jung-Sun; Edwin, Samuel S.; Gomez, Ricardo; Draghici, Sorin

    2012-01-01

    Problem The fetal inflammatory response syndrome (FIRS) is considered the counterpart of the systemic inflammatory response syndrome (SIRS), but similarities in their regulatory mechanisms are unclear. This study characterizes the fetal mRNA transcriptome of peripheral leukocytes to identify key biological processes and pathways involved in FIRS. Method of Study Umbilical cord blood from preterm neonates with FIRS (funisitis, plasma IL-6>11 pg/ml; n=10) and neonates with no evidence of inflammation (n=10) was collected at birth. Results Microarray analysis of leukocyte RNA revealed differential expression of 541 unique genes, changes confirmed by qRT-PCR for 41 or of 44 genes tested. Similar to SIRS and sepsis, ontological and pathway analyses yielded significant enrichment of biological processes including antigen processing and presentation, immune response, and processes critical to cellular metabolism. Results are comparable with microarray studies of endotoxin challenge models and pediatric sepsis, identifying 25 genes across all studies. Conclusions This study is the first to profile genome-wide expression in FIRS, which demonstrates a substantial degree of similarity with SIRS despite differences in fetal and adult immune systems. PMID:20059468

  20. Systemic inflammatory response syndrome and surgical stress in thoracic surgery.

    Science.gov (United States)

    Takenaka, Kazumasa; Ogawa, Eiji; Wada, Hiromi; Hirata, Toshiki

    2006-03-01

    To evaluate the clinical usefulness of postoperative systemic inflammatory response syndrome (SIRS) as an index of surgical stress in patients undergoing thoracic surgery. Forty-five consecutive patients who underwent thoracic surgery with thoracotomy were enrolled. The SIRS criteria were examined daily during the first 7 postoperative days. The serum interleukin-6 (IL-6) level, operation time, intraoperative blood loss, amount of thoracic drainage, and C-reactive protein levels were also measured. Sixteen cases were categorized into the SIRS group, whereas 29 cases were categorized into the non-SIRS group. Among the patients who underwent thoracic surgery, the physiological responses of the patients to the surgery, such as serum IL-6 levels and C-reactive protein levels, were significantly higher in the SIRS group than in the non-SIRS group (P = .002 and .024, respectively). The serum IL-6 level on the first postoperative day was an independent factor associated with SIRS (95% CI 1.002-1.041; P = .030). Furthermore, there was a correlation between the number of SIRS days and the duration of the postoperative hospital stay (r = 0.379, P = .012). Our results demonstrated that SIRS reflected the degree of surgical stress, especially thoracotomic procedures, through the IL-6 levels, and affected the postoperative hospital stay. Systemic inflammatory response syndrome can be useful for the postoperative management of patients undergoing thoracic surgery.

  1. Stress-induced inflammatory responses in women: effects of race and pregnancy.

    Science.gov (United States)

    Christian, Lisa M; Glaser, Ronald; Porter, Kyle; Iams, Jay D

    2013-09-01

    African Americans experience preterm birth at nearly twice the rate of whites. Chronic stress associated with minority status is implicated in this disparity. Inflammation is a key biological pathway by which stress may affect birth outcomes. This study examined the effects of race and pregnancy on stress-induced inflammatory responses. Thirty-nine women in the second trimester of pregnancy (19 African American, 20 white) and 39 demographically similar nonpregnant women completed an acute stressor (Trier Social Stress Test). Psychosocial characteristics, health behaviors, and affective responses were assessed. Serum interleukin (IL)-6 was measured at baseline, 45 minutes, and 120 minutes poststressor. IL-6 responses at 120 minutes poststressor were 46% higher in African Americans versus whites (95% confidence interval = 8%-81%, t(72) = 3.51, p = .001). This effect was present in pregnancy and nonpregnancy. IL-6 responses at 120 minutes poststressor tended to be lower (15%) in pregnant versus nonpregnant women (95% confidence interval = -5%-32%, p = .14). Racial differences in inflammatory responses were not accounted for by demographics, psychological characteristics, health behaviors, or differences in salivary cortisol. Pregnant whites showed lower negative affective responses than did nonpregnant women of either race (p values ≤ .007). This study provides novel evidence that stress-induced inflammatory responses are more robust among African American women versus whites during pregnancy and nonpregnancy. The ultimate impact of stress on health is a function of stressor exposure and physiological responses. Individual differences in stress-induced inflammatory responses represent a clear target for continued research efforts in racial disparities in health during pregnancy and nonpregnancy.

  2. Older Age and Worse Nutritional State Were Related with Impaired Inflammatory Response in Elderly Patients

    Directory of Open Access Journals (Sweden)

    R.A. Tuty Kuswardhani

    2016-07-01

    Full Text Available Background: Ageing process is related with multisystem disorders. One of them is immune response impairment. It is imperative to evaluate the association between age and related nutritional status with inflammatory response in elderly patient. Methods: A cross sectional study to evaluate inflammatory response among elderly patients (≥60 years at Geriatric Out-patient Clinic, Sanglah Hospital was conducted. Seventy-two patients were enrolled in the study. Age, nutritional states (body mass index and mini nutritional assessment, and inflammatory markers (interleukin-2 [IL-2] and C-reactive protein [CRP] and other anthropometric as well as laboratory parameters were measured in the study. Results: In the study it was revealed that age has a moderately negative correlation with both of plasma IL-2 and serum CRP levels (R= -0.305, p=0.009; and R= -0.413, p=0.005, respectively. Plasma IL-2 levels were positively correlated with several variables like body mass index (R=0.282, p=0.016, mini nutritional assessment (R=0.237, p=0.045, biceps skin fold (R=0.291, p=0.013, and triceps skin fold (R=0.258, p=0.028. While serum CRP levels has positive correlation with lying diastolic blood pressure (R=0.345, p=0.020 and negative correlation with calf circumference (R=-0.312, p=0.037. No significant associations were found between diabetes and hypertension with inflammatory markers. Conclusion: This study concluded that older age and worse nutritional state were related to worse inflammatory response in the elderly patients.

  3. Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Wellington Bandeira da Silva

    2009-12-01

    grandes vacúolos. De forma geral, a inoculação de BCG em cascavéis desencadeia respostas inflamatórias hematológicas caracterizadas pela participação de trombócitos, granulócitos e azurófilos.The high demand for anti-venom production in response to the increased number of cases of snakebite envenomation highlights the importance of raising and breeding venomous snakes in captivity. Knowledge of types of venoms and anti-venoms is of great interest to public health. The maintenance of venomous serpents in captivity started in the early twentieth century, but still nowadays it is a challenge to manage and prevent diseases in captive fauna. Hematology is commonly used for general health assessment and illness detection. However, data on serpent blood analysis are still scarce. Alterations in hematological parameters were experimentally induced in rattlesnakes by the inoculation of BCG. Based on this, hemograms can be used as a health auxiliary diagnosis method for bacterial diseases in this species. In this study, blood samples were taken from 10 healthy specimens of rattlesnakes (Crotalus durissus born and bred in captivity in the Herpetological Division of Vital Brazil Institute. Animals were divided into two groups (group 1 and 2 with similar live weight and sex proportion, and were then inoculated subcutaneously with BCG (Bacillus Calmette-Guérin. Blood samples were taken before and after inoculation at three experimental times (days 3, 5 and 7 for group 1 and days 11, 17 and 21 for group 2. Hematological analysis was performed through semi-direct technique, blood samples were diluted in Natt and Herrick solution and smears were stained by Giemsa. Serpents from group 1 developed discrete anemia due to the inflammatory syndrome, and showed significant decrease of MCH and MCHC. Granulocytes were characterized by the presence of rough granules. The azurophils varied in shape and size and showed large amount of cytoplasmic vacuoles. The thrombocytopenia observed

  4. The burn wound inflammatory response is influenced by midazolam.

    Science.gov (United States)

    Babcock, George F; Hernandez, Laura; Yadav, Ekta; Schwemberger, Sandy; Dugan, Amy

    2012-02-01

    Burn patients requiring hospitalization are often treated for anxiety with benzodiazepines (BDZs). Benzodiazepines are reported to influence immune system function. Immune system alterations are a major cause of burn-induced mortality. We wanted to determine whether the BDZ, midazolam given daily at an anxiolytic dose, had any influence on the burn injury-induced inflammatory response in the blood and wound. Mice received a 15% total body surface area flame burn and received either midazolam 1 mg/kg i.p. or saline 0.1 ml daily. Blood and skin wounds were harvested 24 h after injection on post-burn day 2, 3, 7, or 8. Mice treated with midazolam had significantly lower serum IL-1β (p=0.002), TNF-α (p=0.002), IL-6 (p=0.016), IL-10 (p=0.009), and TGF-β (p=0.004) than saline-treated mice, with little impact on serum chemokine levels. In the wound, TNF-α and IL-10 were the only cytokines significantly influenced by the drug, being lower (p=0.018) and higher (p=0.006), respectively. The chemokines in the wound influenced significantly by midazolam were MIP-1α, MIP-1β, and MIP-2 while MCP-1 and KC were not. There were more inflammatory cells at the burn wound margin in midazolam-treated mice on post-burn day 3. Although serum nitrate/nitrite was significantly increased by midazolam (p=0.03), both eNOS and iNOS mRNA expression in the wound were similar to the saline group. We found that midazolam given daily after burn injury significantly influenced the inflammatory response. The clinical implications of these findings on wound healing and shock following burn injury, especially larger burns, deserve further investigation.

  5. Responsive Assessment: Assessing Student Nurses' Clinical Competence.

    Science.gov (United States)

    Neary, Mary

    2001-01-01

    A study involving 300 nursing students, 155 nurse practitioners, and 80 assessors tested a model of responsive assessment that includes identification of learning needs and potential, assignment to suitable placements, continuous assessment of clinical practice and patient care, and alignment of teaching and assessment with patient needs and…

  6. Effect of ghrelin on inflammatory response in lung contusion.

    Science.gov (United States)

    Guven, Berrak; Gokce, Mertol; Saydam, Ozkan; Can, Murat; Bektas, Sibel; Yurtlu, Serhan

    2013-02-01

    The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300-400 g) were randomly assigned into three groups: control group (n = 6), lung contusion plus saline (saline-treated, n = 12), and lung contusion plus ghrelin (ghrelin-treated, n = 12). Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours) after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA). Tissue transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-2 (MMP-2) levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

  7. Inflammatory and bone remodeling responses to the cytolethal distending toxins.

    Science.gov (United States)

    Belibasakis, Georgios N; Bostanci, Nagihan

    2014-04-04

    The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  8. Renal inflammatory response to urinary tract infection in rat neonates.

    Science.gov (United States)

    Zarepour, M; Moradpoor, H; Emamghorashi, F; Owji, S M; Roodaki, M; Khamoushi, M

    2015-09-01

    Urinary tract infection (UTI) is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley) were included in study. The rats were divided into two groups (six rats in each group). In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth). In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1%) showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response.

  9. Renal inflammatory response to urinary tract infection in rat neonates

    Directory of Open Access Journals (Sweden)

    M Zarepour

    2015-01-01

    Full Text Available Urinary tract infection (UTI is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley were included in study. The rats were divided into two groups (six rats in each group. In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth. In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1% showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response.

  10. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis

    Science.gov (United States)

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317

  11. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

    Directory of Open Access Journals (Sweden)

    Georgios N. Belibasakis

    2014-04-01

    Full Text Available The cytolethal distending toxins (CDTs are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  12. Assessment of Sonoelastography as Diagnosis Tool of Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Carolina BOTAR-JID

    2010-12-01

    Full Text Available Background: Inflammatory myopathies represent a special group of pathology. Establishing the correct diagnosis in the early phase and a better follow-up are the main objective for improving the life quality of these patients. Objective: The aim of this research was to assess the usefulness of sonoelastography in diagnosis of inflammatory myopathies. Material and Method: A prospective longitudinal study with a control group was carried out in the Radio-Imaging Department, Cluj-Napoca District University Hospital, Romania, from May 2007 to July 2010. Measurements: Image Processing 2.8 software was used to analyze the elastographic images in correlation with clinical and biochemical data was used. Results: Analysis of Receiver Operating Characteristic curves statistics for elastography parameters showed significant values for the following parameters: average green color, average blue color, average intensity of color, dispersion of red, dispersion of green, and dispersion of hue. Conclusions: Our study highlighted the utility of some elastography parameters in the diagnosis of inflammatory myopathies; the parameter proved to be statistically different in case group compared to control. Anyway, standardization of sonoelastography and larger studies are required to ensure accurate diagnosis, reproductibility and reliability.

  13. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy

    NARCIS (Netherlands)

    Fant, F.; Tina, E.; Sandblom, D.; Andersson, S. -O.; Magnuson, A.; Hultgren-Hornkvist, E.; Axelsson, K.; Gupta, A.

    2013-01-01

    Background. Epidural anaesthesia and analgesia has been shown to suppress the neurohormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropu

  14. Clinical significance of scoring system for systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    HAN Jian; LIANG Hua-ping

    2006-01-01

    The concepts of systemic inflammatory response syndrome (SIRS) and scoring system were defined by the journal of Bone in 1992. SIRS was described as occurrence of two or more clinical criteria in four ones (fever or hypothermia, tachypnea, tachycardia, and leukocytosis).An early diagnosis and estimation of systemic inflammation in patients is helpful for treatment selection. This paper reviews the application of SIRS scoring system, which has been extensively validated for large groups of critical care patients with severe injury and critical surgical diseases.Recent studies have documented SIRS score as a significant predictive parameter of adverse outcome in critical care patients. Furthermore, some studies also give us a suggestion on how to reduce the overload systemic response.

  15. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  16. Innate immune response to pulmonary contusion: identification of cell type-specific inflammatory responses.

    Science.gov (United States)

    Hoth, J Jason; Wells, Jonathan D; Yoza, Barbara K; McCall, Charles E

    2012-04-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.

  17. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

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    Pei Wen Lim

    2016-01-01

    Full Text Available Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals.

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

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

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

  19. Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

    Science.gov (United States)

    2015-10-15

    inflammatory phase of wound healing , and decrease the granulation layer thickness. We propose this modification in the early inflammatory response will also...between p38MAPK signaling, wound inflammatory response, wound healing and long-term scar formation using a burn model in the female red Duroc pig...brief list of keywords (limit to 20 words). Wounds , Burn, topical, wound healing , inflammatory signaling, Mitogen activated protein kinase

  20. Cardiovascular and inflammatory response to cholecystokinin during endotoxemic shock.

    Science.gov (United States)

    Saia, Rafael Simone; Bertozi, Giuliana; Mestriner, Fabíola Leslie; Antunes-Rodrigues, José; Queiróz Cunha, Fernando; Cárnio, Evelin Capellari

    2013-01-01

    Cholecystokinin (CCK) was first described as a gastrointestinal hormone, but its receptors have been located in cardiac and vascular tissues, as well as in immune cells. Our aims were to investigate the role of CCK on lipopolysaccharide (LPS)-induced hypotension and its ability to modulate previously reported inflammatory mediators, therefore affecting cardiovascular function. To conduct these experiments, rats had their jugular vein cannulated for drug administration, and also, the femoral artery cannulated for mean arterial pressure (MAP) and heart rate records. Endotoxemia induced by LPS from Escherichia coli (1.5 mg/kg; i.v.) stimulated the release of CCK, a progressive drop in MAP, and increase in heart rate. Plasma tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), nitrate, vasopressin, and lactate levels were elevated in the endotoxemic rats. The pretreatment with proglumide (nonselective CCK antagonist; 30 mg/kg; i.p.) aggravated the hypotension and also increased plasma TNF-α and lactate levels. On the other hand, CCK (0.4 μg/kg; i.v.) administered before LPS significantly restored MAP, reduced aortic and hepatic inducible nitric oxide synthase (iNOS) production, and elevated plasma vasopressin and IL-10 concentrations; it did not affect TNF-α. Physiological CCK concentration reduced nitrite and iNOS synthesis by peritoneal macrophages, possibly through a self-regulatory IL-10-dependent mechanism. Together, these data suggest a new role for the peptide CCK in modulating MAP, possibly controlling the inflammatory response, stimulating the anti-inflammatory cytokine, IL-10, and reducing vascular and macrophage iNOS-derived nitric oxide production. Based on these findings, CCK could be used as an adjuvant therapeutic agent to improve cardiovascular function.

  1. VARIABILITY OF LEUKOCYTE COUNT AS AN INFLAMMATORY RESPONSE AMONG HYPERTENSIVES

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    Brinda

    2015-12-01

    Full Text Available INTRODUCTION Hypertension, a globally prevailing non communicable disease has been linked to various pathophysiological mechanisms. The new spotlight is on the inflammatory mechanism, which has been embarked on this study by utilising the White blood cell counts as the predominant marker. The pathogenesis behind this concept is the endothelial alteration which occurs in hypertension, causing increased oxidative stress and release of inflammatory mediators and further causing damage to the vascular walls and may result in sustained hypertension. OBJECTIVE To substantiate the difference in leukocyte count among the hypertensives and normotensives, to assess the variation in the leukocyte count among varied grades of hypertension. METHODS 80 subjects and 40 controls of both sex and age between 20-60 years were taken. Subjects with other chronic medical disorders, pregnancy, menstruation phase, history of infections in past 3 months, obesity, smokers and regular alcoholics were excluded. Three recordings of blood pressure were measured with a standard mercury sphygmomanometer. The differential leukocyte count was estimated with an automated counter. RESULTS Statistical analysis was done using independent sample t-test and one-way ANOVA. Total Leukocyte count (Mean = 8397.50 ± 1666.57 was raised significantly among the hypertensives, with P value <0.001. Comparison was done on the total count with the varied hypertensive years, which was suggestive of increase in total count among the pre hypertensives (systolic pressure and there was linear increase in total count with diastolic pressure though not statistically significant. CONCLUSION The elevation of white blood cell count is suggestive of underlying inflammatory mechanism among the hypertensives. The onset of inflammation could be at the onset of hypertension, as there is rise in total leukocyte count among the pre hypertensives which could also lead to sustained hypertension.

  2. Inflammatory response in Colombian children with severe protein-energymalnutrition before and after nutritional intervention

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    Claudia Velasquez

    2010-06-01

    Full Text Available Aim: To evaluate the changes in C-reactive protein and pro-inflammatory cytokines in severely malnourished children, before nutritional intervention and at the moment of restoring appetite. Methodology: To assess changes in inflammatory mediators, 20 severely malnourished children under 5 years of age, 10 with kwashiorkor and 10 with marasmus were studied. Hemoglobin, total serum proteins, albumin, ferritin, transferrin, ceruloplasmin, C-reactive protein and pro-inflammatory cytokines (IL-8, IL-1β, IL-6,IL-10,TNF-α, and IL-12p70 were determined. Results: Upon hospital admission, the mean values of C-reactive protein in kwashiorkor and marasmus patients (16.3±19.0 mg/l and 23.1±27.9 mg/l, respectively indicated an inflammatory response process with no difference between both groups (p=1.0. Total protein, albumin, transferrin and ceruloplasmin in children with kwashiorkor were significantly lower than in marasmic children (p=0.003, p=0.007, p=0.035, p=0.007, respectively. All cytokines, except IL-12p70, showed significantly higher concentrations in kwashiorkor than in marasmic children. After the stabilization phase, concentrations of C-reactive protein decreased significantly in both groups and albumin increased to normal values, but cytokines remained high. Conclusion: These results show that malnourished children are able to synthesize C-reactive protein in response to an infectious process. Additionally, higher levels of pro-inflammatory cytokines and depletion of albumin in children with kwashiorkor suggest that these inflammatory mediators could be critical biomarkers during clinical phases of kwashiorkor.

  3. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  4. Ozone promotes regeneration by regulating the inflammatory response in zebrafish.

    Science.gov (United States)

    Hao, Kenan; Li, Yanhao; Feng, Jianyu; Zhang, Wenqing; Zhang, Yiyue; Ma, Ning; Zeng, Qingle; Pang, Huajin; Wang, Chunyan; Xiao, Lijun; He, Xiaofeng

    2015-09-01

    Ozone is thought to advance wound healing by inhibiting inflammation, but the mechanism of this phenomenon has not been determined. Although the zebrafish is often used in regeneration experiments, there has been no report of zebrafish treated with ozonated water. We successfully established a zebrafish model of ozonated water treatment and demonstrate that ozonated water stimulates the regeneration of the zebrafish caudal fin, its mechanism, and time dependence. The growth rate of the caudal fin and the number of neutrophils migrating to the caudal fin wound after resection were higher in the experimental (ozonated) group than in the control group, preliminarily confirming that ozone-promoted regeneration is related to the stimulation of an early inflammatory response by ozone. Ozone modulated the expression of tumor necrosis factor-α (TNF-α) in two ways by regulating interleukin 10 (IL-10) expression. Therefore, ozone promotes tissue regeneration by regulating the inflammatory pathways. This effect of ozone in an experimental zebrafish model is demonstrated for the first time, confirming its promotion of wound healing and the mechanism of its effect in tissue regeneration. These results will open up new directions for ozone and regeneration research.

  5. Biomechanical changes in endothelial cells result from an inflammatory response

    Science.gov (United States)

    Vaitkus, Janina; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    During periods of infection and disease, the immune system induces the release of TNF-α, an inflammatory cytokine, from a variety of cell types, such as macrophages. TNF-α, while circulating in the vasculature, binds to the apical surface of endothelial cells and causes a wide range of biological and mechanical changes to the endothelium. While the biological changes have been widely studied, the biomechanical aspects have been largely unexplored. Here, we investigated the biomechanical changes of the endothelium as a function of TNF-α treatment. First, we studied the traction forces applied by the endothelium, an effect that is much less studied than others. Through the use of traction force microscopy, we found that TNF-α causes an increase in traction forces applied by the endothelial cells as compared to non-treated cells. Then, we investigated cell morphology, cell mechanics, migration, and cytoskeletal dynamics. We found that in addition to increasing applied traction forces, TNF-α causes an increase in cell area and aspect ratio on average, as well as a shift in the organization of F-actin filaments within the cell. Combining these findings together, our results show that an inflammatory response heavily impacts the morphology, cell mechanics, migration, cytoskeletal dynamics, and applied traction forces of endothelial cells.

  6. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets

    Science.gov (United States)

    Kim, Jong Youl; Kawabori, Masahito; Yenari, Midori A.

    2014-01-01

    Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke. Introduction Stroke refers to conditions caused by occlusion and/or rupture of blood vessels in the brain, and is a leading cause of death and disability in the industrialized world. PMID:24372209

  7. Caspase-12 and the inflammatory response to Yersinia pestis.

    Science.gov (United States)

    Ferwerda, Bart; McCall, Matthew B B; de Vries, Maaike C; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A B; Tissingh, Rudi A; Reubsaet, Frans A G; Sauerwein, Robert; van der Meer, Jos W M; van der Ven, André J A M; Netea, Mihai G

    2009-09-01

    Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.

  8. The Role of Protein Arginine Methyltransferases in Inflammatory Responses

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    Ji Hye Kim

    2016-01-01

    Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

  9. Regulation of inflammatory responses by IL-17F

    Science.gov (United States)

    Yang, Xuexian O.; Chang, Seon Hee; Park, Heon; Nurieva, Roza; Shah, Bhavin; Acero, Luis; Wang, Yi-Hong; Schluns, Kimberly S.; Broaddus, Russell R.; Zhu, Zhou; Dong, Chen

    2008-01-01

    Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases. PMID:18411338

  10. Androgen deprivation modulates the inflammatory response induced by irradiation

    Directory of Open Access Journals (Sweden)

    Lin Paul-Yang

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to determine whether radiation (RT-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies. Methods The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2, TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT -induced fibrosis. Results We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis. Conclusion When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.

  11. Cortisol Response to Low-Dose (1 μg ACTH Stimulation for the Prediction of Outcome in Patients with Systemic Inflammatory Response Syndrome

    Directory of Open Access Journals (Sweden)

    Bjekić-Macut Jelica

    2016-10-01

    Full Text Available Background: Systemic inflammatory response syndrome (SIRS changes cortisol dynamics and indicates dissociation between the adrenal cortex and the hypothalamo-pituitary unit. The aim of this study was to assess the cortisol response after stimulation with ACTH1-24 in patients with SIRS at admission to the Respiratory Intensive Care Unit (RICU and seven days later.

  12. Potentiation of indomethacin-induced anti-inflammatory response by montelukast in formalin-induced inflammation in rats.

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    Ali Asghar Hemmati

    2013-10-01

    Full Text Available The leukotrienes and prostaglandins are biologically active metabolites derived from arachidonic acid. The leukotrienes have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowel disease and asthma. Montelukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. The present study aimed to assess the role of cysteinyl leukotriene receptor antagonist on peripheral inflammation and whether montelukast treatment enhances the anti-inflammatory effect of indomethacin. Anti-inflammatory response was measured using a plethysmometer. Histopathologic examination for leukocyte accumulation was done. Montelukast (0.5-2mg/kg, i.p. produced a significant anti-inflammatory effect in dose dependent manner against formalin-induced rat paw oedema at 1h but not in 3 and 5 h. When indomethacin (5 mg/kg, i.p was co-administered with montelukast (1 mg/kg, i.p, the anti-inflammatory effects of indomethacin were significantly increased as compared to the per se effect at 3 and 5 hour after formalin challenge. In histopathology it has been found that combination therapy significantly decreased migration of leucocytes into the site of inflammation. These results show that montelukast has anti-inflammatory properties in peripheral tissue and markedly potentiates the anti-inflammatory activity of indomethacin at 3 and 5 h. It is expected that combination of montelukast with cyclooxygenase inhibitor would prove to be a novel approach to manage complex inflammatory conditions.

  13. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

    Science.gov (United States)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inflammatory response in laparoscopic vs. open surgery for gastric cancer

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Goetze, Jens Peter; Svendsen, Lars Bo

    2014-01-01

    lead to an increased susceptibility to complications and morbidity. The aim of this review was to investigate if laparoscopic surgery reduces the immunological response compared to open surgery in gastric cancer. METHODS: We conducted a literature search identifying relevant studies comparing......OBJECTIVE: Laparoscopic surgery may offer advantages compared to open surgery, such as earlier mobilization, less pain and lower post-surgical morbidity. Surgical stress is thought to be associated with the postoperative immunological changes in the body as an impaired immune function, which may...... laparoscopy or laparoscopic-assisted surgery with open gastric surgery. The main outcome was postoperative immunological status defined as surgical stress parameters, including inflammatory cytokines and blood parameters. RESULTS: We identified seven studies that addressed the immunological status in patients...

  15. TRAF-mediated regulation of immune and inflammatory responses

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family consists of six mammalian members,and is shown to participate in signal transduction of a large number of receptor families including TNF receptor family (TNFR) and Toll-like receptors-interleukin-1 receptors (TLR-IL-1R) family.Upon receptor activation,TRAFs are directly or indirectly recruited to the intracellular domains of these receptors.They subsequently engage other signaling proteins to activate inhibitor of κB kinase (IKK) complex,TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and inducible I κB kinase (IKK-i) (also known as IKKε),ultimately leading to activation of transcription factors such as NF-κB and interferon-regulatory factor (IRF) to induce immune and inflammatory responses.

  16. Systemic Inflammatory Response Syndrome and postoperative complications after orthognathic surgery.

    Science.gov (United States)

    Kasahara, Kiyohiro; Yajima, Yasutomo; Ikeda, Chihaya; Kamiyama, Isao; Takaki, Takashi; Kakizawa, Takashi; Shibahara, Takahiko

    2009-02-01

    Symptoms of Systemic Inflammatory Response Syndrome (SIRS) presenting immediately after surgery have lately been regarded as potential warnings of impending postoperative complications and multiple organ failure. Reports discussing the relationship between operative stress and SIRS are found in the field of digestive surgery, but not in that of oral surgery. Sixty-five patients with jaw deformity who had undergone maxillary and mandibular orthognathic surgery (Le Fort I osteotomy and sagittal splitting ramus osteotomy) between September 2003 and October 2006 were involved in this study. A search based on the SIRS diagnostic criteria resulted in assignment of 33 cases to the SIRS group and 32 cases to the non-SIRS group. Postoperative complications occurred in 27.3% of the SIRS group and 0.0% of the non-SIRS group (pSIRS patients in preventing complications.

  17. Patterns of inflammatory responses and parasite tolerance vary with malaria transmission intensity.

    Science.gov (United States)

    Ademolue, Temitope W; Aniweh, Yaw; Kusi, Kwadwo A; Awandare, Gordon A

    2017-04-11

    In individuals living in malaria-endemic regions, parasitaemia thresholds for the onset of clinical symptoms vary with transmission intensity. The mechanisms that mediate this relationship are however, unclear. Since inflammatory responses to parasite infection contribute to the clinical manifestation of malaria, this study investigated inflammatory cytokine responses in children with malaria from areas of different transmission intensities (ranging from low to high). Blood samples were obtained from children confirmed with malaria at community hospitals in three areas with differing transmission intensities. Cytokine levels were assessed using the Luminex(®)-based magnetic bead array system, and levels were compared across sites using appropriate statistical tests. The relative contributions of age, gender, parasitaemia and transmission intensity on cytokine levels were investigated using multivariate regression analysis. Parasite density increased with increasing transmission intensity in children presenting to hospital with symptomatic malaria, indicating that the parasitaemia threshold for clinical malaria increases with increasing transmission intensity. Furthermore, levels of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-6, IL-8, and IL-12, decreased with increasing transmission intensity, and correlated significantly with parasitaemia levels in the low transmission area but not in high transmission areas. Similarly, levels of anti-inflammatory cytokines, including IL-4, IL-7, IL-10 and IL-13, decreased with increasing transmission intensity, with IL-10 showing strong correlation with parasitaemia levels in the low transmission area. Multiple linear regression analyses revealed that transmission intensity was a stronger predictor of cytokine levels than age, gender and parasitaemia. Taken together, the data demonstrate a strong relationship between the prevailing

  18. Characterization of the inflammatory response during Ehrlich ascitic tumor development.

    Science.gov (United States)

    Fernandes, Patrícia Dias; Guerra, Fabiana S; Sales, Natália M; Sardella, Thais B; Jancar, Sonia; Neves, Josiane S

    2015-01-01

    Ehrlich tumor is a mammary adenocarcinoma with aggressive behavior. Inoculated in mice peritoneal cavity, the Ehrlich tumor grows in ascitic form (EAT). Since inflammation modulates tumor progression we further investigated the inflammatory response during EAT growth. Balb/C mice were intraperitoneal inoculated with 5×10(5) Ehrlich cells and after every 2days, blood samples were collected for hemoglobin, hematocrit, platelets and leukocytes counts. The ascitic fluid was collected for protein concentration and cell count. Phenotype analysis of the peritoneal cells was made by FACS, prostaglandin E2 (PGE2) and cytokines by ELISA, nitric oxide (NO) by nitrate conversion protocol, and cyclooxygenase-1 (COX1), COX2 and inducible nitric oxide synthase (iNOS) by immunoblotting. Following EAT inoculation into the peritoneal cavity there was a rapid increase in ascitis volume and protein concentration. The cell number in ascitis remained stable until day 8 (lag phase) followed by a sharp increase. As tumor progressed, blood leukocytes increased and erythrocyte decreased. Phenotypic analysis showed that during the lag phase the percentage of F4/80(+) cells remained similar to control levels and around 7% of this population was also positive for the GR1 marker. These double-positive cells (probably inflammatory monocytes) markedly increased at day 6. The percentage of F4/80-GR1(+)cells (probably neutrophils) was low and did not significantly vary during tumor progression. CD4(+) and CD8(+) cells were not detected in the time points analyzed. iNOS and COX1 expression increased after day 2 reaching peak levels on day 10. COX2 enzyme expression did not change significantly over time. Sustained increase in PGE2 and NO levels was observed. IL-10 and MCP-1 peaked at day 14 and IL-1β increased progressively till day 10. IFN-γ levels were low till day 10, increasing progressively after that. These data extended the characterization of the inflammatory response during Ehrlich

  19. Relationship between Inflammatory Response and Estimated Complication Rate after Total Hip Arthroplasty

    Institute of Scientific and Technical Information of China (English)

    Xu-Xu Chen; Tao Wang; Jian Li; Hui Kang

    2016-01-01

    Background:After total hip arthroplasty (THA),there is a noteworthy inflammatory response.The inflammatory response is associated with postoperative recovery and complications.However,there had been few reports on the relationship between inflammatory response and postoperative complication rate.The aim of the present study was to investigate early inflammatory response in the first 3 days after THA,and to identify the relationship between inflammatory response and estimated complication rate after surgery.Methods:It was a prospective,nonrandomized cohort study.There were 148 patients who underwent unilateral THA in our hospital enrolled.Blood samples were collected preoperatively in the morning of the surgery and at 24,48,and 72 h after surgery.C-reactive protein (CRP) and interleukin-6 (IL-6) in peripheral blood were measured.The modified physiological and operative severity score for the enumeration of the morbidity (POSSUM) was recorded pre-and intra-operatively.Based on the score,estimated complication rate was calculated.Harris score was used to assess hip function before and after surgery.Results:IL-6 levels reached the peak at 24 h after surgery and CRP at 48 h.After that,both of the levels decreased.The mean Harris scores significantly increased from 41.62 ± 23.47 before surgery to 72.75 ± 9.13 at 3 days after surgery.The Harris scores after surgery did not have a significant relation with either IL-6 or CRP peak levels (P=0.165,P =0.34 l,respectively).Both CRP and IL-6 peak levels significantly and positively correlated with estimated complication rate after surgery.The estimated complication rate calculated using the POSSUM system was 43 cases of 148 patients.Actually,there were only 28 cases that were observed to get postoperative complications during hospitalization.However,there was no significant difference between estimated and observed complication rates (P =0.078).In the group with complications,the CRP and IL-6 peak levels were significantly

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

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    Feng Yonghui

    2012-08-01

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

  1. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  2. Gut response induced by weaning in piglet features marked changes in immune and inflammatory response.

    Science.gov (United States)

    Bomba, Lorenzo; Minuti, Andrea; Moisá, Sonia J; Trevisi, Erminio; Eufemi, Elisa; Lizier, Michela; Chegdani, Fatima; Lucchini, Franco; Rzepus, Marcin; Prandini, Aldo; Rossi, Filippo; Mazza, Raffaele; Bertoni, Giuseppe; Loor, Juan J; Ajmone-Marsan, Paolo

    2014-12-01

    At weaning, piglets are exposed to many stressors, such as separation from the sow, mixing with other litters, end of lactational immunity, and a change in their environment and gut microbiota. The sudden change of feeding regime after weaning causes morphological and histological changes in the small intestine which are critical for the immature digestive system. Sixteen female piglets were studied to assess the effect of sorbic acid supplementation on the small intestine tissue transcriptome. At weaning day (T0, piglet age 28 days), four piglets were sacrificed and ileal tissue samples collected. The remaining 12 piglets were weighed and randomly assigned to different postweaning (T5, piglet age 33 days) diets. Diet A (n = 6) contained 5 g/kg of sorbic acid. In diet B (n = 6), the organic acids were replaced by barley flour. Total RNA was isolated and then hybridized to CombiMatrix CustomArray™ 90-K platform microarrays, screening about 30 K genes. Even though diet had no detectable effect on the transcriptome during the first 5 days after weaning, results highlighted some of the response mechanisms to the stress of weaning occurring in the piglet gut. A total of 205 differentially expressed genes were used for functional analysis using the bioinformatics tools BLAST2GO, Ingenuity Pathway Analysis 8.0, and Dynamic Impact Approach (DIA). Bioinformatic analysis revealed that apoptosis, RIG-I-like, and NOD-like receptor signaling were altered as a result of weaning. Interferons and caspases gene families were the most activated after weaning in response to piglets to multiple stressors. Results suggest that immune and inflammatory responses were activated and likely are a cause of small intestine atrophy as revealed by a decrease in villus height and villus/crypt ratio.

  3. TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

    Science.gov (United States)

    Fernandez-Gonzalo, Rodrigo; De Paz, José A; Rodriguez-Miguelez, Paula; Cuevas, María J; González-Gallego, Javier

    2014-01-01

    This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-β-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.

  4. TLR4-Mediated Blunting of Inflammatory Responses to Eccentric Exercise in Young Women

    Science.gov (United States)

    De Paz, José A.; Rodriguez-Miguelez, Paula; Cuevas, María J.

    2014-01-01

    This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-β-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population. PMID:25294957

  5. Strain Assessment in Surgically Resected Inflammatory and Neoplastic Bowel Lesions

    DEFF Research Database (Denmark)

    Havre, R F; Leh, S; Gilja, O H

    2014-01-01

    Purpose: To investigate whether ultrasound-based strain imaging can discriminate between colorectal adenocarcinomas and stenotic Crohn's lesions in newly resected surgical specimens.Materials and Methods: Resected surgical specimens from 27 patients electively operated for colorectal tumors...... or stenotic lesions from Crohn's disease were prospectively examined with ultrasonography using a Hitachi HV 900 US scanner with real-time elastography (RTE). Three different methods were applied to assess tissue strain: A four-level categorical visual classification, a continuous visual analog scale (VAS, 0...... - 100) and a strain ratio (SR) measurement between the lesion and surrounding reference tissue. The imaged sections were marked and subsequently examined by a pathologist. Results from RTE were evaluated according to diagnosis, degree of fibrosis, inflammatory parameters, tumor stage and grade...

  6. The laminin response in inflammatory bowel disease: protection or malignancy?

    Directory of Open Access Journals (Sweden)

    Caroline Spenlé

    Full Text Available Laminins (LM, basement membrane molecules and mediators of epithelial-stromal communication, are crucial in tissue homeostasis. Inflammatory Bowel Diseases (IBD are multifactorial pathologies where the microenvironment and in particular LM play an important yet poorly understood role in tissue maintenance, and in cancer progression which represents an inherent risk of IBD. Here we showed first that in human IBD colonic samples and in murine colitis the LMα1 and LMα5 chains are specifically and ectopically overexpressed with a concomitant nuclear p53 accumulation. Linked to this observation, we provided a mechanism showing that p53 induces LMα1 expression at the promoter level by ChIP analysis and this was confirmed by knockdown in cell transfection experiments. To mimic the human disease, we induced colitis and colitis-associated cancer by chemical treatment (DSS combined or not with a carcinogen (AOM in transgenic mice overexpressing LMα1 or LMα5 specifically in the intestine. We demonstrated that high LMα1 or LMα5 expression decreased susceptibility towards experimentally DSS-induced colon inflammation as assessed by histological scoring and decrease of pro-inflammatory cytokines. Yet in a pro-oncogenic context, we showed that LM would favor tumorigenesis as revealed by enhanced tumor lesion formation in both LM transgenic mice. Altogether, our results showed that nuclear p53 and associated overexpression of LMα1 and LMα5 protect tissue from inflammation. But in a mutation setting, the same LM molecules favor progression of IBD into colitis-associated cancer. Our transgenic mice represent attractive new models to acquire knowledge about the paradoxical effect of LM that mediate either tissue reparation or cancer according to the microenvironment. In the early phases of IBD, reinforcing basement membrane stability/organization could be a promising therapeutic approach.

  7. Food Restriction Affects Inflammatory Response and Nutritional State in Tuco-tucos (Ctenomys talarum).

    Science.gov (United States)

    Merlo, Julieta Leticia; Cutrera, Ana Paula; Zenuto, Roxana Rita

    2016-12-01

    Insufficient or unbalanced food intake typically has a negative impact on immune responses. The understanding of this effect is, however, hampered by the effect that food has on general condition, which, in turn, affects immunity, and the interaction among general condition, immunocompetence, and concurrent infections. The goal of this study was to determine the effects of food restriction and methionine supplementation on immunity in tuco-tucos (Ctenomys talarum). Effects of diet manipulations on nutritional state, inflammatory response to phytohemagglutinin (PHA), and other immune parameters (bacterial killing capacity, natural antibodies, and leukocyte profile) were evaluated. Health and stress parameters and endoparasite loads were assessed to understand more deeply potential effects of treatments on immune status. Individuals under food restriction presented an altered nutritional state as well as increased stress levels (higher N: L ratios) compared with individuals fed ad libitum, and a marked reduction in the inflammatory response to PHA. Supplementation with methionine did not affect any of the parameters analyzed. Endoparasite loads were not affected by treatments. Our results support the idea that food insufficiency can modulate the individual's immune responsiveness through the lack of adequate essential nutrients, metabolic fuel and energetic reserves, or by a detrimental effect of the stress caused by nutrient limitation. We show that the response to PHA previously reported as nonenergetically costly for C. talarum, implies a nutritional cost; an opposite pattern to that previously found for the adaptive antibody response to sheep red blood cells in the same species.

  8. Subclinical inflammatory response after accelerated corneal cross-linking

    Institute of Scientific and Technical Information of China (English)

    Hassan Hashemi; Nahid Ashraf; Ebrahim Jafarzadehpur; Alireza Hedayatfar; Soheila Asgari

    2016-01-01

    Background: To evaluate the inlfammatory response after accelerated collagen cross-linking (CXL) in eyes with keratoconus. Methods: Consecutive eyes with keratoconus undergoing CXL surgery were included in this non-randomized interventional study. Aqueous lfare was measured pre- and post-operatively with a laser lfare photometer at 1 week, 1, 3 and 6 months after CXL. Results: Sixty eyes of 60 patients were entered into the study. Before CXL, the mean lfare value was 4.5 photons per millisecond (ph/ms). The lfare values observed at week 1 (7.1 ph/ms; P=0.008), month 1 (6.5 ph/ms; P=0.04), month 3 (6.7 ph/ms; P=0.004) and month 6 (6.7 ph/ms; P=0.004) were signiifcantly higher compared to baseline. Flare values were not signiifcantly different from week 1 up to 6 months after CXL (P=0.930). No statistically significant correlation was detected between the amount of inlfammation and keratometric indices. Conclusions: Accelerated CXL in patients with keratoconus may cause a subclinical inflammatory response which is evident as slight but rather long-lasting rise of aqueous lfare.

  9. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

    Directory of Open Access Journals (Sweden)

    Ruidong Li

    2016-01-01

    Full Text Available Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS. Maresin 1 (Mar1 is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β. Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT, aspartate transaminase (AST, creatinine (Cre, and blood urea nitrogen (BUN in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

  10. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    Science.gov (United States)

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  11. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Na-Young Park

    2010-01-01

    Full Text Available Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA, a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage. We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

  12. Apoptosis of resident and inflammatory macrophages before and during the inflammatory response of the virgin bovine mammary gland

    Directory of Open Access Journals (Sweden)

    Sladek Zbysek

    2010-02-01

    Full Text Available Abstract Background Macrophages may play a prominent role in defense of the bovine mammary gland, and their functionality is necessary for successful eradication of bacterial pathogens. In contrast to necrosis, however, apoptosis has not yet been studied in macrophages from bovine mammary glands. Therefore, the aim of this study was to confirm the occurrence of apoptosis in macrophages from resting heifer mammary glands and during the inflammatory response. Methods Inflammatory response was induced by phosphate buffered saline (PBS and by lipopolysaccharide (LPS. Resident macrophages (RESMAC were obtained before and inflammatory macrophages (INFMAC 24, 48, 72 and 168 hours after inducing inflammatory response in mammary glands of unbred heifers. Cell samples were analyzed for differential counts, apoptosis and necrosis using flow cytometry. Results Populations of RESMAC and INFMAC contained monocyte-like cells and vacuolized cells. Apoptosis was detected differentially in both morphologically different types of RESMAC and INFMAC and also during initiation and resolution of the inflammatory response. In the RESMAC population, approximately one-tenth of monocyte-like cells and one-third of vacuolized cells were apoptotic. In the INFMAC population obtained 24 h after PBS treatment, approximately one-tenth of monocyte-like cells and almost one-quarter of vacuolized cells were apoptotic. At the same time following LPS, however, we observed a significantly lower percentage of apoptotic cells in the population of monocyte-like INFMAC and vacuolized INFMAC. Moreover, a higher percentage of apoptotic cells in INFMAC was detected during all time points after PBS in contrast to LPS. Comparing RESMAC and INFMAC, we observed that vacuolized cells from populations of RESMAC and INFMAC underwent apoptosis more intensively than did monocyte-like cells. Conclusions We conclude that apoptosis of virgin mammary gland macrophages is involved in regulating their

  13. HELLP syndrome is associated with an increased inflammatory response, which may be inhibited by administration of prednisolone.

    NARCIS (Netherlands)

    Heimel, PJ van Runnard; Kavelaars, A.; Heijnen, C.J.; Peters, W.H.M.; Huisjes, A.J.M.; Franx, A.; Bruinse, H.W.

    2008-01-01

    OBJECTIVE: To investigate the effect of prednisolone on HELLP syndrome by assessing several markers of the inflammatory response and hepatic damage associated with HELLP syndrome. DESIGN: Prospective study. SETTING: Single-center, tertiary obstetric care facility at the University Medical Centre Utr

  14. HELLP syndrome is associated with an increased inflammatory response, which may be inhibited by administration of prednisolone

    NARCIS (Netherlands)

    Heimel, Pieter J. van Runnard; Kavelaars, Annemiek; Heijnen, Cobie J.; Peters, Wilbert H. M.; Huisjes, Anjoke J. M.; Franx, Arie; Bruinse, Hein W.

    2008-01-01

    Objective. To investigate the effect of prednisolone on HELLP syndrome by assessing several markers of the inflammatory response and hepatic damage associated with HELLP syndrome. Design. Prospective study. Setting. Single-center, tertiary obstetric care facility at the University Medical Centre Utr

  15. HELLP syndrome is associated with an increased inflammatory response, which may be inhibited by administration of prednisolone

    NARCIS (Netherlands)

    Heimel, Pieter J. van Runnard; Kavelaars, Annemiek; Heijnen, Cobie J.; Peters, Wilbert H. M.; Huisjes, Anjoke J. M.; Franx, Arie; Bruinse, Hein W.

    2008-01-01

    Objective. To investigate the effect of prednisolone on HELLP syndrome by assessing several markers of the inflammatory response and hepatic damage associated with HELLP syndrome. Design. Prospective study. Setting. Single-center, tertiary obstetric care facility at the University Medical Centre Utr

  16. Instillation of coarse ash particulate matter and lipopolysaccharide produces a systemic inflammatory response in mice

    Energy Technology Data Exchange (ETDEWEB)

    Finnerty, K.; Choi, J.E.; Lau, A.; Davis-Gorman, G.; Diven, C.; Seaver, N.; Linak, W.P.; Witten, M.; McDonagh, P.F. [Arizona Health Science Center, Tucson, AZ (United States)

    2007-07-01

    Coronary ischemic events increase significantly following a 'bad air' day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM > 2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 {mu} g), PM+ LPS10 (PM+ 10 {mu} g LPS), or PM+ LPS100 (PM+ 100 {mu} g LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-{alpha} and IL-6 both increased significantly with PM+ LPS100 treatment. Regarding plasma, TNF-{alpha} significantly increased in both PM+ LPS10 and PM+ LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM+ LPS100 group. The results of the follow-up study indicate that the responses to PM+ LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM > 2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.

  17. The hemic response of white-spotted bamboo sharks (Chiloscyllium plagiosum) with inflammatory disease.

    Science.gov (United States)

    Alexander, Amy B; Parkinson, Lily A; Grant, Krystan R; Carlson, Eric; Campbell, Terry W

    2016-05-01

    As elasmobranch medicine becomes more commonplace, there continues to be confusion with techniques and evaluation of the shark hemogram and it remains unknown if they are able to mount an inflammatory hemic response. The aims of this study were to compare two total white blood cell (WBC) count techniques, establish a reference interval for captive white-spotted bamboo sharks (Chiloscyllium plagiosum), and determine if elasmobranchs are capable of mounting an inflammatory hemic response. Correlation statistics were performed on hematologic results for healthy female bamboo sharks to assess the use of Natt-Herrick's and phloxine methods. Total WBC counts and differentials were obtained from males with severe traumatic clasper wounds and compared to the healthy females. We elected clasper amputation as the preferred treatment intervention and post-operative hematology was performed one month later. There was poor correlation of leukocyte counts between the two WBC count methods. Hematologic values were established for the females and males pre- and post-operatively. Males with wounds had a marked leukocytosis and heterophilia. Post-operative blood work showed a resolution of total WBC count and a trend toward resolution of the heterophilia. This study provides hematologic values for white-spotted bamboo sharks and confirms that the Natt-Herrick's method is preferred for lymphocytic species. Hematologic differences present in males with clasper wounds suggests that elasmobranchs do mount an inflammatory hemic response. Treatment via clasper amputation proved to be a safe and efficient means for clinical treatment that led to a trend toward resolution of the inflammatory leukogram. Zoo Biol. 35:251-259, 2016. © 2016 Wiley Periodicals, Inc.

  18. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

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    D. Remirez

    2002-01-01

    Full Text Available It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300 mg/kg post-orally (p.o. was administered 1 h before the challenge with 1 μg of ovalbumin (OA in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o. also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phyco-cyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

  19. Shikonin Inhibits Inflammatory Response in Rheumatoid Arthritis Synovial Fibroblasts via lncRNA-NR024118

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    Ke-ya Yang

    2015-01-01

    Full Text Available Background. Shikonin is a major chemical component of zicao that possesses anti-inflammatory properties and the ability to mediate cellular and humoral immunity, especially in rheumatoid arthritis (RA. We investigated the impact of shikonin on inflammatory response in RA synovial fibroblasts using the CAIA model. Methods. Severe polyarticular arthritis was induced in Balb/c female mice. Expressions of lncRNA-NR024118, SOCS3, proinflammatory cytokines, and MMPs were evaluated using RT-RCR. Histone acetylation and SOCS3 protein expression were assessed by ChIP assay and western blot, respectively. Results. Mice treated with shikonin showed an abrogation of soft tissue and bone lesions. Shikonin remarkably enhanced the expression of NR024118 and SOCS3 and suppressed the secretion and expression of IL-6, IL-8, and MMPs. Proliferation of cultured RA synovial fibroblasts in the presence of IL-1β was also significantly inhibited by shikonin. Moreover, shikonin dose-dependently increased acetylation of histone H3 at the promoter of NR024118. Finally, NR024118 overexpression and interference significantly changed SOCS3 expression and NR024118 interference could reverse regulation of shikonin on SOCS3, proinflammatory cytokines, and MMPs expression level in MH7A cells. Conclusion. Our results reveal that, in the CAIA mouse model of RA, shikonin has disease modifying activity that is attributable to the inhibition of inflammatory response via lncRNA-NR024118.

  20. Experimental obstructive cholestasis: the wound-like inflammatory liver response

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    Aller María-Angeles

    2008-11-01

    Full Text Available Abstract Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

  1. Role of Fiber Length on Phagocytosis & Inflammatory Response

    Science.gov (United States)

    Turkevich, Leonid; Stark, Carahline; Champion, Julie

    2014-03-01

    Asbestos fibers have long been associated with lung cancer death. The inability of immune cells (e.g. macrophages) to effectively remove asbestos leads to chronic inflammation and disease. This study examines the role of fiber length on toxicity at the cellular level using model glass fibers. A major challenge is obtaining single diameter fibers but differing in length. Samples of 1 micron diameter fibers with different length distributions were prepared: short fibers (less than 15 microns) by aggressive crushing, and long fibers (longer than 15 microns) by successive sedimentation. Time-lapse video microscopy monitored the interaction of MH-S murine alveolar macrophages with the fibers: short fibers were easily internalized by the macrophages, but long fibers resisted internalization over many hours. Production of TNF- α (tumor necrosis factor alpha), a general inflammatory secreted cytokine, and Cox-2 (cyclo-oxygenase-2), an enzyme that produces radicals, each exhibited a dose-dependence that was greater for long than for short fibers. These results corroborate the importance of fiber length in both physical and biochemical cell response and support epidemiological observations of higher toxicity for longer fibers.

  2. Tourniquet-induced systemic inflammatory response in extremity surgery.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    BACKGROUND: Tourniquet-induced reperfusion injury in animals produces significant systemic inflammatory effects. This study investigated whether a biologic response occurs in a clinically relevant model of tourniquet-induced reperfusion injury. METHODS: Patients undergoing elective knee arthroscopy were prospectively randomized into controls (no tourniquet) and subjects (tourniquet-controlled). The effects of tourniquet-induced reperfusion on monocyte activation state, neutrophil activation state, and transendothelial migration (TEM) were studied. Changes in the cytokines implicated in reperfusion injury, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-10 were also determined. RESULTS: After 15 minutes of reperfusion, neutrophil and monocyte activation were significantly increased. Pretreatment of neutrophils with pooled subject (ischemia-primed) plasma significantly increased TEM. In contrast, TEM was not significantly altered by ischemia-primed plasma pretreatment of the endothelial monolayer. Significant elevation of tumor necrosis factor-alpha and IL-1beta were observed in subjects compared with controls after 15 minutes of reperfusion. There was no significant difference in serum IL-10 levels between the groups at all the time points studied. CONCLUSION: These results indicate a transient neutrophil and monocyte activation after tourniquet-ischemia that translates into enhanced neutrophil transendothelial migration with potential for tissue injury.

  3. Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

    Science.gov (United States)

    Lins, Nara; Mourão, Luiz; Trévia, Nonata; Passos, Aline; Farias, José Augusto; Assunção, Jarila; Bento-Torres, João; Consentino Kronka Sosthenes, Marcia; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa

    2016-01-01

    We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits. PMID:28003864

  4. Is leptin related to systemic inflammatory response in acute pancreatitis?

    Institute of Scientific and Technical Information of China (English)

    Andrés Duarte-Rojo; Ana Lezama-Barreda; Mar(i)a Teresa Ram(i)rez-lglesias; Mario Peláez Luna; Guillermo Robles-Diaz

    2006-01-01

    AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-α, IL-6, -8and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.RESULTS: Fifty-two (29 females) patients were studied.Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6.Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

  5. Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury

    Science.gov (United States)

    Zhang, Qin; Raoof, Mustafa; Chen, Yu; Sumi, Yuka; Sursal, Tolga; Junger, Wolfgang; Brohi, Karim; Itagaki, Kiyoshi; Hauser, Carl J.

    2009-01-01

    Injury causes a systemic inflammatory response syndrome (SIRS) clinically much like sepsis 1. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors 2. Similarly, cellular injury can release endogenous damage-associated molecular patterns (DAMPs) that activate innate immunity 3. Mitochondria are evolutionary endosymbionts that were derived from bacteria 4 and so might bear bacterial molecular motifs. We show here that injury releases mitochondrial DAMPs (MTD) into the circulation with functionally important immune consequences. MTD include formyl peptides and mitochondrial DNA. These activate human neutrophils (PMN) through formyl peptide receptor-1 and TLR9 respectively. MTD promote PMN Ca2+ flux and phosphorylation of MAP kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTD can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These can then signal through identical innate immune pathways to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation and SIRS. PMID:20203610

  6. Impact of Mycotoxins Secreted by Aspergillus Molds on the Inflammatory Response of Human Corneal Epithelial Cells

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    Yélian Marc Bossou

    2017-06-01

    Full Text Available Exposure to molds and mycotoxins not only contributes to the onset of respiratory disease, it also affects the ocular surface. Very few published studies concern the evaluation of the effect of mycotoxin exposure on ocular cells. The present study investigates the effects of aflatoxin B1 (AFB1 and gliotoxin, two mycotoxins secreted by Aspergillus molds, on the biological activity of the human corneal epithelial (HCE cells. After 24, 48, and 72 h of exposure, cellular viability and inflammatory response were assessed. Both endpoint cell viability colorimetric assays and continuous cell impedance measurements, providing noninvasive real-time assessment of the effect on cells, were performed. Cytokine gene expression and interleukin-8 release were quantified. Gliotoxin appeared more cytotoxic than AFB1 but, at the same time, led to a lower increase of the inflammatory response reflecting its immunosuppressive properties. Real-time cell impedance measurement showed a distinct profile of cytotoxicity for both mycotoxins. HCE cells appeared to be a well-suited in vitro model to study ocular surface reactivity following biological contaminant exposure. Low, but persistent inflammation, caused by environmental factors, such as fungal toxins, leads to irritation and sensitization, and could be responsible for allergic manifestations which, in turn, could lead to mucosal hyper-reactivity.

  7. Anti-inflammatory effect of Taraxacum officinale leaves on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells.

    Science.gov (United States)

    Koh, Yoon-Jeoung; Cha, Dong-Soo; Ko, Je-Sang; Park, Hyun-Jin; Choi, Hee-Don

    2010-08-01

    To investigate the efficacy and the mechanism of the anti-inflammatory effect of Taraxacum officinale leaves (TOLs), the effect of a methanol extract and its fractions recovered from TOLs on lipopolysaccharide (LPS)-induced responses was studied in the mouse macrophage cell line, RAW 264.7. Cells were pretreated with various concentrations of the methanol extract and its fractions and subsequently incubated with LPS (1 microg/mL). The levels of nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined using enzyme-linked immunosorbent assays. Expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and activation of mitogen-activated protein (MAP) kinases were analyzed using western blotting. The methanol extract and its fractions inhibited LPS-induced production of NO, pro-inflammatory cytokines, and PGE(2) in a dose-dependent manner. The chloroform fraction significantly suppressed production of NO, PGE(2), and two pro-inflammatory cytokines (TNF-alpha and IL-1beta) in a dose-dependent manner with 50% inhibitory concentration values of 66.51, 90.96, 114.76, and 171.06 microg/mL, respectively. The ethyl acetate fraction also inhibited production of the inflammatory molecules. The chloroform and ethyl acetate fractions reduced LPS-induced expressions of iNOS and COX-2 and activation of MAP kinases in a dose-dependent manner. Among the fractions of the methanol extract, the chloroform and ethyl acetate fractions exhibited the most effective anti-inflammatory activities. These results show that the anti-inflammatory effects of TOLs are probably due to down-regulation of NO, PGE(2), and pro-inflammatory cytokines and reduced expressions of iNOS and COX-2 via inactivation of the MAP kinase signal pathway.

  8. Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide

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    Santos-Galindo María

    2011-07-01

    Full Text Available Abstract Background Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response. Methods Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10, TNFα, IL1β, Toll-like receptor 4 (TLR4, steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpaired t-test or by one-way analysis of variance followed by the Tukey post hoc test. Results The mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to

  9. Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in an experimental pulmonary thromboembolism model.

    Science.gov (United States)

    Deng, Chaosheng; Zhai, Zhenguo; Wu, Dawen; Lin, Qichang; Yang, Yuanhua; Yang, Minxia; Ding, Haibo; Cao, Xiaoming; Zhang, Qiaoxian; Wang, Chen

    2015-07-01

    Lung ischemia-reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. The inflammatory response mechanisms related to LIRI in pulmonary thromboembolism (PTE), especially in chronic PTE, need to be studied further. In a PTE model, inflammatory response and apoptosis may occur during LIRI and nitric oxide (NO) inhalation may alleviate the inflammatory response and apoptosis of pneumocytes during LIRI. A PTE canine model was established through blood clot embolism to the right lower lobar pulmonary artery. Two weeks later, we performed embolectomy with reperfusion to examine the LIRI changes among different groups. In particular, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), serum concentrations of tumor necrosis factor-α (TNF-α), myeloperoxidase concentrations in lung homogenates, alveolar polymorphonuclear neutrophils (PMNs), lobar lung wet to dry ratio (W/D ratio), apoptotic pneumocytes, and lung sample ultrastructure were assessed. The PaO2/FiO2 in the NO inhalation group increased significantly when compared with the reperfusion group 4 and 6 h after reperfusion (368.83 ± 55.29 vs. 287.90 ± 54.84 mmHg, P inflammatory response and apoptosis occur in our PTE model and NO inhalation may be useful in treating LIRI by alleviating the inflammatory response and pneumocyte apoptosis. This potential application warrants further investigation.

  10. Endocannabinoids and inflammatory response in periodontal ligament cells.

    Directory of Open Access Journals (Sweden)

    Burcu Özdemir

    Full Text Available Endocannabinoids are associated with multiple regulatory functions in several tissues. The main endocannabinoids, anandamide (AEA and 2-arachidonylglycerol (2-AG, have been detected in the gingival crevicular fluid of periodontitis patients, but the association between periodontal disease or human periodontal ligament cells (hPdLCs and endocannabinoids still remain unclear. The aim of the present study was to examine the effects of AEA and 2-AG on the proliferation/viability and cytokine/chemokine production of hPdLCs in the presence/absence of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS. The proliferation/viability of hPdLCs was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT-assay. Interleukin-6 (IL-6, interleukin-8 (IL-8, and monocyte chemotactic protein-1 (MCP-1 levels were examined at gene expression and protein level by real-time PCR and ELISA, respectively. AEA and 2-AG did not reveal any significant effects on proliferation/viability of hPdLCs in the absence of P. gingivalis LPS. However, hPdLCs viability was significantly increased by 10-20 µM AEA in the presence of P. gingivalis LPS (1 µg/ml. In the absence of P. gingivalis LPS, AEA and 2-AG did not exhibit any significant effect on the expression of IL-8 and MCP-1 expression in hPdLCs, whereas IL-6 expression was slightly enhanced by 10 µM 2-AG and not affected by AEA. In P.gingivalis LPS stimulated hPdLCs, 10 µM AEA down-regulated gene-expression and protein production of IL-6, IL-8, and MCP-1. In contrast, 10 µM 2-AG had an opposite effect and induced a significant up-regulation of gene and protein expression of IL-6 and IL-8 (P<0.05 as well as gene-expression of MCP-1 in P. gingivalis LPS stimulated hPdLCs. Our data suggest that AEA appears to have an anti-inflammatory and immune suppressive effect on hPdLCs' host response to P.gingivalis LPS, whereas 2-AG appears to promote detrimental inflammatory processes. In conclusion

  11. Endocannabinoids and inflammatory response in periodontal ligament cells.

    Science.gov (United States)

    Özdemir, Burcu; Shi, Bin; Bantleon, Hans Peter; Moritz, Andreas; Rausch-Fan, Xiaohui; Andrukhov, Oleh

    2014-01-01

    Endocannabinoids are associated with multiple regulatory functions in several tissues. The main endocannabinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG), have been detected in the gingival crevicular fluid of periodontitis patients, but the association between periodontal disease or human periodontal ligament cells (hPdLCs) and endocannabinoids still remain unclear. The aim of the present study was to examine the effects of AEA and 2-AG on the proliferation/viability and cytokine/chemokine production of hPdLCs in the presence/absence of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS). The proliferation/viability of hPdLCs was measured using 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT)-assay. Interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) levels were examined at gene expression and protein level by real-time PCR and ELISA, respectively. AEA and 2-AG did not reveal any significant effects on proliferation/viability of hPdLCs in the absence of P. gingivalis LPS. However, hPdLCs viability was significantly increased by 10-20 µM AEA in the presence of P. gingivalis LPS (1 µg/ml). In the absence of P. gingivalis LPS, AEA and 2-AG did not exhibit any significant effect on the expression of IL-8 and MCP-1 expression in hPdLCs, whereas IL-6 expression was slightly enhanced by 10 µM 2-AG and not affected by AEA. In P.gingivalis LPS stimulated hPdLCs, 10 µM AEA down-regulated gene-expression and protein production of IL-6, IL-8, and MCP-1. In contrast, 10 µM 2-AG had an opposite effect and induced a significant up-regulation of gene and protein expression of IL-6 and IL-8 (P<0.05) as well as gene-expression of MCP-1 in P. gingivalis LPS stimulated hPdLCs. Our data suggest that AEA appears to have an anti-inflammatory and immune suppressive effect on hPdLCs' host response to P.gingivalis LPS, whereas 2-AG appears to promote detrimental inflammatory processes. In conclusion, AEA and 2

  12. Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions.

    Science.gov (United States)

    Takei, Miwa; Kobayashi, Makiko; Herndon, David N; Pollard, Richard B; Suzuki, Fujio

    2006-09-01

    In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.

  13. Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation

    NARCIS (Netherlands)

    Oliveira, M.C.; Silveira, A.L.; Tavares, L.P.; Rodrigues, D.F.; Loo, F.A.J. van de; Sousa, L.P.; Teixeira, M.M.; Amaral, F.A.; Ferreira, A.V.

    2017-01-01

    OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known a

  14. Systemic inflammatory response to exhaustive exercise in patients with chronic obstructive pulmonary disease.

    NARCIS (Netherlands)

    Helvoort, H.A.C. van; Pol, M.H.J. van de; Heijdra, Y.F.; Dekhuijzen, P.N.R.

    2005-01-01

    Systemic inflammation may be present in patients with chronic obstructive pulmonary disease (COPD). Exercise is known to elicit an inflammatory response. We hypothesized that the systemic inflammatory response to exercise might be exaggerated in COPD patients compared to healthy subjects. Sixteen CO

  15. Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa

    NARCIS (Netherlands)

    Hyseni, A.; Kemperman, H.; De Lange, D. W.; De Groot, P. G.; Linssen, M.; Kesecioglu, J.; Lisman, T.; Roest, M.

    2013-01-01

    BackgroundThe tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a c

  16. Whole-body MRI for full assessment and characterization of diffuse inflammatory myopathy

    Directory of Open Access Journals (Sweden)

    Saleh Saleh Elessawy

    2016-09-01

    Full Text Available Background Conventional magnetic resonance imaging (MRI is a highly valuable tool for full assessment of the extent of bilateral symmetrical diffuse inflammatory myopathy, owing to its high sensitivity in the detection of edema which correlates with, and sometimes precedes, clinical findings. Purpose To evaluate the use of whole-body (WB-MRI in characterization and full assessment of the extent and distribution of diffuse inflammatory myopathy. Material and Methods A prospective study on 15 patients presenting with clinical evidence of inflammatory myopathy. It included 4 boys/men and 11 girls/women (age range, 6–44 years; mean age, 25.5 years. 1.5 T WB-MRI was performed and the distribution and extent of disease severity was assessed according to muscle edema on STIR images. Results Four cases of dermatomyositis showed lower limb disease predilection with edema in gluteal, thigh, and calf muscles. The same finding was seen in one case with recurrent polymyositis and three cases with overlap myositis with systemic lupus erythematosus (SLE. Bilateral upper and lower limb myositis was demonstrated in three cases of polymyositis and one case of overlap myositis with scleroderma. Bilateral edema involving all scanned muscle groups was detected in three cases of polymyositis with paraneoplastic syndrome, SLE, and severe active dermatomyositis (including the neck muscles. Conclusion WB-MRI is the diagnostic modality of choice for cases of inflammatory myopathy. It accurately detects the most severely affected muscles candidate for biopsy and provides a reliable baseline study for follow-up of disease progression as well as response to treatment.

  17. Xanthohumol suppresses inflammatory response to warm ischemia-reperfusion induced liver injury.

    Science.gov (United States)

    Dorn, Christoph; Massinger, Sabine; Wuzik, Andreas; Heilmann, Jörg; Hellerbrand, Claus

    2013-02-01

    Liver ischemia/reperfusion (I/R) leads to formation of reactive oxygen species (ROS), which cause hepatic injury and initiate an inflammatory response, which is a critical problem after liver surgery and transplantation. Xanthohumol, the major prenylated chalcone found in hops, has been discussed for its anti-inflammatory and ROS-scavenging properties, and thus, we aimed to investigate the effect of xanthohumol in a model of warm I/R liver injury. Xanthohumol was applied to BALB/c mice orally at a dose of 1 mg/g body weight for 5 days before I/R-injury was induced by clamping the vascular blood supply to the median and left lateral liver lobe for 1 h followed by a 6 h period of reperfusion. At this time, HPLC analysis revealed hepatic xanthohumol levels of approximately 2 μM, a concentration which has been shown to inhibit inflammatory effects in vitro. Assessment of hepatic HMOX1 expression, hepatic glutathione content and immunohistochemical analysis for proteins conjugated with the reactive aldehyde 4-hydroxynonenal indicated that I/R-induced oxidative stress was significantly inhibited in xanthohumol-fed compared to control mice. Histological analysis, TUNEL staining and determination of transaminase serum levels revealed no significant effects of xanthohumol on acute hepatocellular injury. However, at the same time point, pretreatment with xanthohumol almost completely blunted the I/R-induced AKT and NFκB activation and the expression of the proinflammatory genes IL-1alpha, IL-6, MCP-1 and ICAM-1, which are known to play a crucial role in the subacute phase of I/R-induced liver damage. In conclusion, these data indicate the potential of xanthohumol application to prevent adverse inflammatory responses to I/R-induced liver damage such as after surgical liver resection or transplantation.

  18. Salicornia bigelovii Torr Attenuates Neuro-Inflammatory Responses ...

    African Journals Online (AJOL)

    BV- microglial cells were stimulated with LPS to study the protein expression and .... complete culture medium and treated with the. SBE extract .... and pathological processes leading to increased inflammatory .... Nutritional characterization of.

  19. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  20. Lactic acid delays the inflammatory response of human monocytes.

    Science.gov (United States)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Prokineticin 1 Induces Inflammatory Response in Human Myometrium

    Science.gov (United States)

    Gorowiec, Marta R.; Catalano, Rob D.; Norman, Jane E.; Denison, Fiona C.; Jabbour, Henry N.

    2011-01-01

    The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C-C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E2 and F2α secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. PMID:21983634

  2. Mangiferin ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in mouse model of postoperative ileus.

    Science.gov (United States)

    Morais, Talita Cavalcante; Arruda, Bruno Rodrigues; de Sousa Magalhães, Hebert; Trevisan, Maria Teresa Salles; de Araújo Viana, Daniel; Rao, Vietla Satyanarayana; Santos, Flavia Almeida

    2015-05-01

    Our previous study has shown that mangiferin (MGF), a glucosylxanthone from Mangifera indica, exerts gastrointestinal prokinetic action involving a cholinergic mechanism. Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. The present study investigated to know whether MGF having anti-inflammatory and prokinetic actions can ameliorate the intestinal inflammation and impaired gastrointestinal transit seen in the mouse model of POI. Experimental POI was induced in adult male Swiss mice by standardized small intestinal manipulation (IM). Twenty-four hours later, gastrointestinal transit was assessed by charcoal transport. MGF was administered orally 1 h before the measurement of GIT. To evaluate the inflammatory response, plasma levels of proinflammatory cytokines TNF-α, IL-1β, IL-6, and chemokine MCP-1, and the myeloperoxidase activity, nitrate/nitrite level, and histological changes of ileum were determined in mice treated or not with MGF. Experimental POI in mice was characterized by decreased gastrointestinal transit and marked intestinal and systemic inflammatory response. MGF treatment led to recovery of the delayed intestinal transit induced by IM. MGF in ileum significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration, and nitrate/nitrite level and reduced the plasma levels of TNF-α, IL-1β, IL-6, and MCP-1 as well. MGF treatment ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in the mouse model of POI.

  3. Asian dust particles induce macrophage inflammatory responses via mitogen-activated protein kinase activation and reactive oxygen species production.

    Science.gov (United States)

    Higashisaka, Kazuma; Fujimura, Maho; Taira, Mayu; Yoshida, Tokuyuki; Tsunoda, Shin-ichi; Baba, Takashi; Yamaguchi, Nobuyasu; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Nasu, Masao; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2014-01-01

    Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor- α (TNF- α ) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10  μ m in diameter provoked a greater inflammatory response than soil dust samples containing particles >10  μ m. In addition, Asian dust particles-induced TNF- α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor- κ B and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages.

  4. Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

    Directory of Open Access Journals (Sweden)

    Kazuma Higashisaka

    2014-01-01

    Full Text Available Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-α (TNF-α compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10 μm in diameter provoked a greater inflammatory response than soil dust samples containing particles >10 μm. In addition, Asian dust particles-induced TNF-α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-κB and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages.

  5. Salvianolic acid B inhibits platelets-mediated inflammatory response in vascular endothelial cells.

    Science.gov (United States)

    Xu, Shixin; Zhong, Aiqin; Bu, Xiaokun; Ma, Huining; Li, Wei; Xu, Xiaomin; Zhang, Junping

    2015-01-01

    Salvianolic acid B (SAB) is a hydrophilic component isolated from the Chinese herb Salviae miltiorrhizae, which has been used clinically for the treatment of ischemic cardiovascular and cerebrovascular diseases. Platelets-mediated vascular inflammatory response contributes to the initiation and progression of atherosclerosis. In this paper, we focus on the modulating effects of SAB on the inflammatory reaction of endothelial cells triggered by activated platelets. Human umbilical vein endothelial cells (EA.hy926) were pretreated with SAB followed by co-culture with ADP-activated platelets. Adhesion of platelets to endothelial cells was observed by amorphological method. The activation of nuclear factor-kappa B was evaluated by NF-κB p65 nuclear translocation and the protein phosphorylation. A determination of the pro-inflammatory mediators (ICAM-1, IL-1β, IL-6, IL-8, MCP-1) mRNA and protein were also conducted. In addition, the inhibitory effects of SAB on platelets activation were also evaluated using a platelet aggregation assay and assessing the release level of soluble P-selectin. The results showed that SAB dose-dependently inhibited ADP- or α-thrombin-induced human platelets aggregation in platelet rich plasma (PRP) samples, and significantly decreased soluble P-selectin release from both agonists stimulated washed platelets. It was also found that pre-treatment with SAB reduced adhesion of ADP-activated platelets to EA.hy926 cells and inhibited NF-κB activation. In addition, SAB significantly suppressed pro-inflammatory mediators mRNA and protein in EA.hy926 cells in a dose-dependent manner. These results indicated that, in addition to its inhibitory effects on platelets activation, SAB was able to attenuate platelets-mediated inflammatory responses in endothelial cells even if the platelets had already been activated. This anti-inflammatory effect was related to the inhibition of NF-κB activation. Our findings suggest that SAB may be a potential

  6. [Clinical profile of systemic inflammatory response after pediatric cardiac surgery with cardiopulmonary bypass].

    Science.gov (United States)

    Soares, Leonardo Cavadas da Costa; Ribas, Denise; Spring, Regine; Silva, Jean Marcelo Ferreira da; Miyague, Nelson Itiro

    2010-01-01

    the postoperative period of congenital cardiomyopathies correction is frequently accompanied by systemic inflammatory response. To assess the frequency of occurrence and clinical manifestations of the systemic inflammatory response syndrome after cardiopulmonary bypass (SIRS-CPB) in children submitted to cardiac surgery. Historical cohort study including patients up to 3 years old that were submitted to elective corrective surgeries for congenital cardiopathies with cardiopulmonary bypass (CPB). A total of 101 patients were assessed by means of clinical criteria of organ dysfunction through score tests, as comparing predisponent factors and aggregated morbidity to the presence of SIRS-CPB. Twenty-two patients (21.9%) fulfilled the criteria for SIRS-CPB. The sex or type of cardiopathy did not differ between groups (p = NS). Patients diagnosed with SIRS-CPB (compared to patients without SIRS-CPB) presented lower mean age (6.8 +/- 5.5 versus 10.8 +/- 5.1 months, p SIRS-CPB, which presented lower weight and longer CPB duration as predisponent factors. Patients with SIRS-CPB remain in mechanical ventilation, in ICU and in hospitalization for a longer period of time.

  7. Inflammatory response in patients undergoing uterine artery embolization as compared to patients undergoing conventional hysterectomy

    DEFF Research Database (Denmark)

    Brøchner, A C; Mygil, B; Elle, B;

    2009-01-01

    : To investigate whether uterine artery embolization generates a reduced inflammatory response as compared with conventional hysterectomy. MATERIAL AND METHODS: 40 women, 20 in each group, entered this prospective, non-randomized study. The two groups were comparable concerning age, comorbidity, and body......-mass index (BMI). RESULTS: We found a significant difference between the inflammatory responses in women undergoing embolization compared with the inflammatory response in women having an abdominal hysterectomy. Women undergoing embolization were subjected to a much smaller inflammatory burden, their total...... morphine consumption was lower, and their return to work was faster than women subjected to conventional hysterectomy. CONCLUSION: Uterine artery embolization generates a reduced inflammatory response compared with conventional hysterectomy....

  8. Systemic inflammatory response syndrome and multiple-organ damage / dysfunction in complicated canine babesiosis

    Directory of Open Access Journals (Sweden)

    C. Welzl

    2001-07-01

    Full Text Available This study was designed to document the systemic inflammatory response syndrome (SIRS and multiple-organ dysfunction syndrome (MODS in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retro-spectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are manysimilarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.

  9. S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection.

    Science.gov (United States)

    Li, Yaling; Xie, Peng; Sun, Minhua; Xiang, Bin; Kang, Yinfeng; Gao, Pei; Zhu, Wenxian; Ning, Zhangyong; Ren, Tao

    2016-01-01

    Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.

  10. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ying [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Li, Shu-Jun [Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Yang, Jian [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Qiu, Yuan-Zhen [Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410078 (China); Chen, Fang-Ping, E-mail: xychenfp@163.com [Department of Hematology, Xiangya Hospital, Central South University, Changsha 410078 (China)

    2013-09-06

    Highlights: •Mechanisms of inflammatory response induced by HMGB1 are incompletely understood. •We found that endoplasmic reticulum stress mediate the inflammatory response induced by HMGB1. •RAGE-mediated ERS pathways are involved in those processes. •We reported a new mechanism for HMGB1 induced inflammatory response. -- Abstract: The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01–1 μg/ml) for 24 h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway.

  11. Limitations in assessment of mucosal healing in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2010-01-01

    An emerging parameter to define the effectiveness of new therapeutic agents in clinical trials,and by extension,for use in day-to-day clinical practice has been labeled mucosal healing.It has been hypothesized that complete healing of the intestinal mucosa in inflammatory bowel diseases should result in reduced disease complications,reduced hospitalization and reduced surgical treatment.By implication,the natural history of inflammatory bowel disease might then be altered. Measurement of mucosal healing,how...

  12. Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

    Directory of Open Access Journals (Sweden)

    Winfried Möller

    Full Text Available Endotoxin (Lipopolysaccharide, LPS is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h, Interleukin-6 (peaking at 6 h, body temperature (peaking at 12 h, and CRP (peaking at 24 h. 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1 and reactive oxygen production, assessed by hydrogen peroxide (H(2O(2 in fractionated exhaled breath condensate (EBC. FEV(1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2O(2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2O(2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

  13. Environmental particulate matter induces murine intestinal inflammatory responses and alters the gut microbiome.

    Directory of Open Access Journals (Sweden)

    Lisa Kish

    Full Text Available BACKGROUND: Particulate matter (PM is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions. METHODS: Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93 for 7-14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10(-/- mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum. RESULTS: Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10(-/- mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10(-/- mice had increased disease as evidenced by enhanced histological damage. CONCLUSIONS: Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine.

  14. Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

    Directory of Open Access Journals (Sweden)

    José Alves Gurgel

    2013-12-01

    Full Text Available Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.] 1 h before the injection of carrageenan (300 μg/0.1 mL/paw or dextran (500 μg/0.1 mL/paw. Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch and N-formyl-methionyl-leucyl-phenylalanine (fMLP (10-6 M/mL/pouch was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01. Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001. Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization.

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

    Directory of Open Access Journals (Sweden)

    M Mojtahedzadeh

    2011-05-01

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

  16. Induction of inflammatory responses from THP-1 cells by cell-free filtrates from clinical isolates of Alloiococcus otitidis.

    Science.gov (United States)

    Ashhurst-Smith, Christopher; Hall, Sharron T; Burns, Christine J; Stuart, John; Blackwell, C Caroline

    2014-04-01

    In our model system using the THP-1 monocytic cell line, whole heat-killed cells of Alloiococcus otitidis elicited several pro-inflammatory cytokines identified in ear effusions of children with otitis media (OM). Levels of these cytokines were equivalent to or greater than those elicited by a standard Gram-positive otopathogen, Streptococcus pneumoniae. The current study examined the hypothesis that extracellular material produced by A. otitidis might also contribute to the inflammatory responses in OM. Cell-free culture filtrates of recent A. otitidis isolates (n = 39) were tested for induction of pro-inflammatory cytokines from THP-1 cells primed with IFN-γ. The highest responses were from IL-8 followed by IL-1β, and the lowest from IL-6. Filtrates from nine isolates were treated with lysozyme or proteinase K to assess the nature of the extracellular stimulants. Peptidoglycan was not a major component eliciting the responses. There was no correlation between colony type or β-haemolysin production. Proteinase K treatment indicated extracellular proteins might induce the inflammatory responses, particularly the 70-75 ku band. Further studies on the role of the extracellular proteins of A. otitidis and cytokine responses in pathogenesis of ear infections are needed.

  17. A new role for T cells in dampening innate inflammatory responses

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The inflammatory response is an attempt by a host to protect itself against injurious stimuli and initiate the tissue healing process [1,2]. Although the production of both pro-and anti-inflammatory mediators which occurs mainly within tissues is a systemic process,

  18. Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

    NARCIS (Netherlands)

    Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

    2013-01-01

    Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the in

  19. Utility of immune response-derived biomarkers in the differential diagnosis of inflammatory disorders

    NARCIS (Netherlands)

    Oever, J. ten; Netea, M.G.; Kullberg, B.J.

    2016-01-01

    Differentiating between inflammatory disorders is difficult, but important for a rational use of antimicrobial agents. Biomarkers reflecting the host immune response may offer an attractive strategy to predict the etiology of an inflammatory process and can thus be of help in decision making. We

  20. The inflammatory response in cardiac surgery: an overview of the pathophysiology and clinical implications.

    Science.gov (United States)

    Corral-Velez, Vicente; Lopez-Delgado, Juan C; Betancur-Zambrano, Nelson L; Lopez-Suñe, Neus; Rojas-Lora, Mariel; Torrado, Herminia; Ballus, Josep

    2015-01-01

    During cardiac surgery different factors, such as the aortic clamp, the extracorporeal circulation and the surgical injury itself, produce complex inflammatory responses which can lead to varying degrees of ischemia-reperfusion injury and/or systemic inflammatory response. This may have clinical implications due to hemodynamic changes related with an enlarged vasodilatory response. Thus, maintaining adequate levels of blood pressure during and after cardiac surgery represents a challenge for physicians when inflammatory response appears. The use of noradrenaline to raise arterial pressure is the most current pharmacological approach in the operating room and ICU. However, it is not always effective and other drugs, such as methylene blue, have to be used among others in specific cases as rescue therapy. The aim of our research is to review briefly the pathophysiology and clinical implications in the treatment of the inflammatory response in cardiac surgery, together with the mechanisms involved in those treatments.

  1. Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents

    NARCIS (Netherlands)

    Haegens, A.; Vernooy, J. H. J.; Heeringa, P.; Mossman, B. T.; Wouters, E. F. M.

    2008-01-01

    During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to characte

  2. Diminazene aceturate (Berenil modulates the host cellular and inflammatory responses to Trypanosoma congolense infection.

    Directory of Open Access Journals (Sweden)

    Shiby Kuriakose

    Full Text Available BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b⁺ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25⁺ cells, a concomitant reduction in the percentage of regulatory (CD4⁺Foxp3⁺ T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm. CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology

  3. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  4. Traumatic Reticuloperitonitis in Water Buffalo (Bubalus bubalis: Clinical Findings and the Associated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Maged El-Ashker

    2013-01-01

    Full Text Available The present study was carried out to describe the clinical picture of traumatic reticuloperitonitis (TRP in water buffalo (Bubalus bubalis and to evaluate the inflammatory and immunologic responses for this clinical condition. Twenty-two buffalo with acute local TRP were monitored in our study. Additionally, 10 clinically healthy buffalo were randomly selected and served as controls. Acute local TRP was initially diagnosed by clinical examination and confirmed by ultrasonographic (USG examination and/or necropsy findings. Blood samples were collected from all examined buffalo to measure the respective levels of tumor necrosis factor alpha (TNF-α, interleukin (IL-1β, IL-6, IL-10 and interferon gamma (INF-γ, serum amyloid A (SAA, C-reactive protein (CRP, haptoglobin (Hp, fibrinogen (Fb, and serum sialic acid (SSA. It was found that TNF-α, IL-1β, IL-6, IL-10, SAA, CRP, Hp, Fb, and SSA were significantly higher in buffalo with TRP than the controls. Our findings suggest that the examined immunologic variables were helpful in documenting the inflammatory response in buffalo with TRP. However, their diagnostic usefulness only becomes apparent when considered in tandem with the clinical findings for any given animal, its anamnesis, and a subsequent USG assessment. Due to the frequent complications of TRP, more accurate indicators of its occurrence and severity would be useful.

  5. Inflammatory cytokine responses in a pregnant mouse model of Chlamydophila abortus infection.

    Science.gov (United States)

    Kerr, Karen; Wheelhouse, Nicholas; Livingstone, Morag; Anderson, Ian E; Entrican, Gary; McKeever, Declan; Longbottom, David

    2010-08-26

    Chlamydophila abortus (C. abortus) is the aetiological agent of ovine enzootic abortion (OEA). The highly elevated expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and low-level expression of interferon-gamma (IFNgamma) that are detected in C. abortus-infected placentas have been implicated in the pathogenesis of OEA. Late-term abortions similar to those occurring in sheep have also been observed in mouse models of C. abortus infection. Since mouse studies have contributed significantly to our understanding of the immunological responses to chlamydial infections and serve as a good model for rapidly assessing candidate vaccines for OEA, we investigated local expression of TNFalpha and IFNgamma in infected mice. At various time points over the course of infection mice were sacrificed, serum samples obtained for serum antibody and cytokine analyses, and livers and placental tissues were removed and fixed to determine C. abortus colonisation and cytokine expression. Immunostaining for C. abortus was significantly greater in placenta compared to liver (P<0.001), whereas local IFNgamma expression was lower and TNFalpha expression was absent in the placenta compared with the liver across all time points. Serum concentrations of both IFNgamma and TNFalpha increased throughout pregnancy in infected mice. These data suggest that a protective systemic inflammatory immune response controls maternal C. abortus infection but not placental/fetal infection in mice. In contrast to sheep, murine placental TNFalpha expression does not correlate with C. abortus infection, suggesting that the immunopathogenesis of chlamydial abortion differs in these species.

  6. Ultrasonic incisions produce less inflammatory mediator response during early healing than electrosurgical incisions.

    Directory of Open Access Journals (Sweden)

    Bindu Nanduri

    Full Text Available As the use of laparoscopic surgery has become more widespread in recent years, the need has increased for minimally-invasive surgical devices that effectively cut and coagulate tissue with reduced tissue trauma. Although electrosurgery (ES has been used for many generations, newly-developed ultrasonic devices (HARMONIC® Blade, HB have been shown at a macroscopic level to offer better coagulation with less thermally-induced tissue damage. We sought to understand the differences between ES and HB at a microscopic level by comparing mRNA transcript and protein responses at the 3-day timepoint to incisions made by the devices in subcutaneous fat tissue in a porcine model. Samples were also assessed via histological examination. ES-incised tissue had more than twice as many differentially-expressed genes as HB (2,548 vs 1,264 respectively, and more differentially-expressed proteins (508 vs 432 compared to control (untreated tissue. Evaluation of molecular functions using Gene Ontology showed that gene expression changes for the energized devices reflected the start of wound healing, including immune response and inflammation, while protein expression showed a slightly earlier stage, with some remnants of hemostasis. For both transcripts and proteins, ES exhibited a greater response than HB, especially in inflammatory mediators. These findings were in qualitative agreement with histological results. This study has shown that transcriptomics and proteomics can monitor the wound healing response following surgery and can differentiate between surgical devices. In agreement with clinical observations, electrosurgery was shown to incur a greater inflammatory immune response than an ultrasonic device during initial iatrogenic wound healing.

  7. The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia?

    Science.gov (United States)

    Stokes, Karen Y; Granger, D Neil

    2005-01-01

    There is abundant evidence that links hypercholesterolaemia to both vascular inflammation and atherogenesis. While atherosclerosis is a large vessel disease that is characterized by leucocyte infiltration and lipid deposition in the wall of lesion-prone arteries, the inflammatory response does not appear to be confined to these locations. There is evidence supporting a systemic inflammatory response that is characterized by endothelial cell activation in multiple vascular beds and the appearance of activated immune cells and a wide range of inflammatory mediators in blood. The mechanism(s) responsible for initiating this systemic response remain poorly defined, although several inciting factors have been proposed, including infectious agents and oxidative stress resulting from one or more of the cardiovascular risk factors (e.g. hypercholesterolaemia, hypertension). While cells within lesion-prone arteries are often inferred as the source of circulating inflammatory mediators during atherogenesis, the fact that endothelial cells throughout the vasculature are activated raises the possibility that the microvasculature (which encompasses a vast endothelial surface area) may contribute to creating the systemic inflammatory milieu that is linked to atherogenesis. This review addresses evidence that links the microvasculature to the inflammatory responses induced by hypercholesterolaemia and offers the hypothesis that inflammatory events initiated within the microcirculation may contribute to initiation and/or progression of large vessel disease. PMID:15611017

  8. Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

    Science.gov (United States)

    Schmid, Alexandra; Petry, Nicolai; Walther, Barbara; Bütikofer, Ueli; Luginbühl, Werner; Gille, Doreen; Chollet, Magali; McTernan, Philip G; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François P; Laederach, Kurt; Vergères, Guy

    2015-06-28

    Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

  9. Infant intestinal Enterococcus faecalis down-regulates inflammatory responses in human intestinal cell lines

    Institute of Scientific and Technical Information of China (English)

    Shugui Wang; Lydia Hui Mei Ng; Wai Ling Chow; Yuan Kun Lee

    2008-01-01

    AIM:To investigate the ability of Lactic acid bacteria (LAB)to modulate inflammatory reaction in human intestinal celllines(Caco-2,HT-29 and HCT 116).Different strains of LAB isolatedfrom new born infants and fermented milk,together withthestrains obtained from culture collectionsweretested.METHODS:LABs were treated with human intestinal cell lines.ELISA was used to detect IL-8 and TGF-β protein secretion.Cytokines and Toll like receptors (TLRs) gene expression were assessed using RT-PCR.Conditional medium,sonicated bacteria and UV killed bacteria were used to find the effecter molecules on the bacteria.Carbohydrate oxidation and protein digestion were applied to figure out the molecules'residues.Adhesion assays were further carried out.RESULTS:It was found that Enterococcus faecalis is the main immune modulator among the LABs by downregulation of IL-8 secretion and upregulation of TGF-β.Strikingly,the effect was only observed in four strains of E.faecalis out of the 27 isolated and tested.This implies strain dependent immunomodulation in the host.In addition,E.faecalis may regulate inflammatory responses through TLR3,TLR4,TLR9 and TRAF6.Carbohydrates on the bacterial cell surface are involved in both its adhesion to intestinal cells and regulation of inflammatory responses in the host.CONCLUSION:These data provide a case for the modulation of intestinal mucosal immunity in which specific strains of E.faecalis have uniquely evolved to maintain colonic homeostasis and regulate inflammatoryresponses.

  10. mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy

    Science.gov (United States)

    Song, Xiaoxiao; Kusakari, Yoichiro; Xiao, Chun-Yang; Kinsella, Stuart D.; Rosenberg, Michael A.; Scherrer-Crosbie, Marielle; Hara, Kenta; Rosenzweig, Anthony

    2010-01-01

    Previous studies have suggested that inhibition of the mammalian target of rapamycin (mTOR) by rapamycin suppresses myocardial hypertrophy. However, the role of mTOR in the progression of cardiac dysfunction in pathological hypertrophy has not been fully defined. Interestingly, recent reports indicate that the inflammatory response, which plays an important role in the development of heart failure, is enhanced by rapamycin under certain conditions. Our aim in this study was to determine the influence of mTOR on pathological hypertrophy and to assess whether cardiac mTOR regulates the inflammatory response. We generated transgenic mice with cardiac-specific overexpression of wild-type mTOR (mTOR-Tg). mTOR-Tg mice were protected against cardiac dysfunction following left ventricular pressure overload induced by transverse aortic constriction (TAC) (P cardiac dysfunction in WT. At 1 wk post-TAC, the proinflammatory cytokines interleukin (IL)-1β and IL-6 were significantly increased in WT mice but not in mTOR-Tg mice. To further characterize the effects of mTOR activation, we exposed HL-1 cardiomyocytes transfected with mTOR to lipopolysaccharide (LPS). mTOR overexpression suppressed LPS-induced secretion of IL-6 (P < 0.001), and the mTOR inhibitors rapamycin and PP242 abolished this inhibitory effect of mTOR. In addition, mTOR overexpression reduced NF-κB-regulated transcription in HL-1 cells. These data suggest that mTOR mitigates adverse outcomes of pressure overload and that this cardioprotective effect of mTOR is mediated by regulation of the inflammatory reaction. PMID:20861467

  11. Therapeutic effects of sesame oil on monosodium urate crystal-induced acute inflammatory response in rats.

    Science.gov (United States)

    Hsu, Dur-Zong; Chen, Si-Jin; Chu, Pei-Yi; Liu, Ming-Yie

    2013-01-01

    Sesame oil has been used in traditional Taiwanese medicine to relieve the inflammatory pain in people with joint inflammation, toothache, scrapes, and cuts. However, scientific evidence related to the effectiveness or action mechanism of sesame oil on relief of pain and inflammation has not been examined experimentally. Here, we investigated the therapeutic effect of sesame oil on monosodium urate monohydrate (MSU) crystal-induced acute inflammatory response in rats. Air pouch, a pseudosynovial cavity, was established by injecting 24 mL of filtered sterile air subcutaneously in the backs of the rats. At day 0, inflammation in air pouch was induced by injecting MSU crystal (5 mg/rat, suspended in sterilized phosphate buffered saline, pH 7.4), while sesame oil (0, 1, 2, or 4 mL/kg, orally) was given 6 h after MSU crystal injection. Parameters in lavage and skin tissue from the air pouches were assessed 6 h after sesame oil was given. Sesame oil decreased MSU crystal-induced total cell counts, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in lavage and pouch tissue. Sesame oil significantly decreased leukocyte and neutrophil counts in lavage compared with MSU crystal alone group. Sesame oil decreased activated mast cell counts in skin tissue in MSU crystal-treated rats. Sesame oil significantly decreased nuclear factor (NF)-κB activity and IL-4 level in isolated mast cells from rats treated with MSU crystal. Furthermore, sesame oil decreased lavage complement proteins C3a and C5a levels in MSU crystal-treated rats. In conclusion, sesame oil shows a potent therapeutic effect against MSU crystal-induced acute inflammatory response in rats.

  12. Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

    DEFF Research Database (Denmark)

    Poulsen, Troels Dirch; Andersen, Lars Willy; Steinbrüchel, Daniel

    2009-01-01

    OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug...... of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery........ This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB. DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital. PARTICIPANTS: Patients scheduled...

  13. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  14. Managing the Inflammatory Response after Cardiopulmonary Bypass : Review of the Studies in Animal Models

    NARCIS (Netherlands)

    Liguori, Gabriel Romero; Kanas, Alexandre Fligelman; Moreira, Luiz Felipe Pinho

    2014-01-01

    OBJECTIVE: To review studies performed in animal models that evaluated therapeutic interventions to inflammatory response and microcirculatory changes after cardiopulmonary bypass. METHODS: It was used the search strategy ("Cardiopulmonary Bypass" (MeSH)) and ("Microcirculation" (MeSH) or "Inflammat

  15. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis

    National Research Council Canada - National Science Library

    Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E

    2015-01-01

    Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations...

  16. Epigallocatechin-3-gallate attenuates lipopolysaccharide-induced mastitis in rats via suppressing MAPK mediated inflammatory responses and oxidative stress.

    Science.gov (United States)

    Chen, Jinglou; Xu, Jun; Li, Jingjing; Du, Lifen; Chen, Tao; Liu, Ping; Peng, Sisi; Wang, Mingwei; Song, Hongping

    2015-05-01

    Green tea (Camellia sinensis) is an extremely popular beverage worldwide. Epigallocatechin-3-gallate (EGCG) is one of the major catechins isolated from green tea and contributes to its beneficial therapeutic functions including antioxidant, anti-inflammatory and anti-cancer effects. However, the effect of EGCG on mastitis is not yet known. This study was to investigate the protective potential of EGCG against mastitis in rats. The rat mastitis model was induced by injecting lipopolysaccharide (LPS) into the duct of mammary gland. The mammary gland was collected after the experimental period. The levels of mammary oxidative stress and inflammatory responses were assessed by measuring the local activities of antioxidant enzymes and the levels of inflammatory cytokines. The mammary expressions of mitogen-activated protein kinases (MAPKs), nuclear factor κB-p65 (NFκB-p65) and hypoxia-inducible factor-1α (HIF-1α) were evaluated by western blot analysis. It was found that EGCG obviously normalized LPS-induced low activities of antioxidant enzymes as well as decreased the high levels of inflammatory cytokines. Additionally, EGCG inhibited the mammary over-expression of MAPKs, NFκB-p65 and HIF-1α. These results indicated that EGCG was able to attenuate LPS-induced mastitis in rats by suppressing MAPK related oxidative stress and inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  18. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Schaapherder, A.F.M.; Bockel, J.H. van; Thüsen, J.H. vonder; Roelen, D.L.; Kleemann, R.

    2008-01-01

    Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in

  19. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    OpenAIRE

    López-González, Miguel A.; Antonio Abrante; Carmen López-Lorente; Antonio Gómez; Emilio Domínguez; Francisco Esteban

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deaf...

  20. [Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer].

    Science.gov (United States)

    Khristich, T N

    2014-11-01

    The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.

  1. Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

    Science.gov (United States)

    Laurent, Heidemarie K; Lucas, Todd; Pierce, Jennifer; Goetz, Stefan; Granger, Douglas A

    2016-07-01

    Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

  2. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...... days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot. RESULTS: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen...... vasoconstrictor response to IS, but not to CFA. CONCLUSIONS: These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system....

  3. The Systemic Inflammatory Response in Patients with Appendicitis: a Progressive Phenomenon.

    Science.gov (United States)

    Beltrán, Marcelo A

    2015-12-01

    The systemic inflammatory response has been described in patients with appendicitis. However, its progression from onset of symptoms to diagnosis has not been characterized. The specific purpose of this study was to describe and characterize the systemic inflammatory response to appendicitis. A descriptive cross-sectional study was conducted. One hundred eighty-three patients were studied, divided into four groups from onset of symptoms to diagnosis. The primary outcome measure was to determine the systemic inflammatory response to appendicitis according to the established groups of time intervals. The secondary outcome measure was the analysis of C-reactive protein for the same purpose. The variables of the systemic inflammatory response, according to diagnostic intervals, showed non-significant differences in white blood cell count. The temperature rose constantly after 48 h, reaching its peak after 72 h (p = 0.001), and the respiratory rate rose after 73 h (p inflammatory response criteria (p inflammatory response to appendicitis is progressive, being more marked along the timeline from onset of symptoms to diagnosis.

  4. Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

    OpenAIRE

    Kazuma Higashisaka; Maho Fujimura; Mayu Taira; Tokuyuki Yoshida; Shin-ichi Tsunoda; Takashi Baba; Nobuyasu Yamaguchi; Hiromi Nabeshi; Tomoaki Yoshikawa; Masao Nasu; Yasuo Yoshioka; Yasuo Tsutsumi

    2014-01-01

    Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to ...

  5. Nutrition before and during Surgery and the Inflammatory Response of the Heart: A Randomized Controlled Trial.

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    Visser, Marlieke; Niessen, Hans W M; Kok, Wouter E M; Cocchieri, Riccardo; Wisselink, Willem; van Leeuwen, Paul A M; de Mol, Bas A J M

    2015-01-01

    Major surgery induces a long fasting time and provokes an inflammatory response which increases the risk of infections. Nutrition given before and during surgery can avoid fasting and has been shown to increase the arginine/asymmetric dimetlhylarginine ratio, a marker of nitric oxide availability, in cardiac tissue and increased concentrations of branched chain amino acids in blood plasma. However, the effect of this new nutritional strategy on organ inflammatory response is unknown. Therefore, we studied the effect of nutrition before and during cardiac surgery on myocardial inflammatory response. In this trial, 32 patients were randomised between enteral, parenteral, and no nutrition supplementation (control) from 2 days before, during, up to 2 days after coronary artery bypass grafting. Both solutions included proteins or amino acids, glucose, vitamins, and minerals. Myocardial atrial tissue was sampled before and after revascularization and was analysed immunohistochemically, subdivided into cardiomyocytic, fatty, and fibrotic areas. Inflammatory cells, especially leukocytes, were present in cardiac tissue in all study groups. No significant differences were found in the myocardial inflammatory response between the enteral, parenteral, and control groups. In conclusion, nutrition given before and during surgery neither stimulates nor diminishes the myocardial inflammatory response in patients undergoing coronary artery bypass grafting. The trial was registered in Netherlands Trial Register (NTR): NTR2183.

  6. Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

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    Shizuka Hirai

    2010-01-01

    Full Text Available Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ, whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB and/or c-Jun amino-terminal kinase (JNK. In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies.

  7. Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2 knock-out mice following stroke.

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    Matthias W Sieber

    Full Text Available BACKGROUND: Triggering receptor expressed on myeloid cells-2 (TREM2 is a microglial surface receptor involved in phagocytosis. Clearance of apoptotic debris after stroke represents an important mechanism to re-attain tissue homeostasis and thereby ensure functional recovery. The role of TREM2 following stroke is currently unclear. METHODS AND RESULTS: As an experimental stroke model, the middle cerebral artery of mice was occluded for 30 minutes with a range of reperfusion times (duration of reperfusion: 6 h/12 h/24 h/2 d/7 d/28 d. Quantitative PCR (qPCR revealed a greatly increased transcription of TREM2 after stroke. We subsequently analyzed the expression of pro-inflammatory cytokines, chemokines and their receptors in TREM2-knockout (TREM2-KO mice via qPCR. Microglial activation (CD68, Iba1 and CD3-positive T-cell invasion were analyzed via qPCR and immunohistochemistry. Functional consequences of TREM2 knockout were assessed by infarct volumetry. The acute inflammatory response (12 h reperfusion was very similar between TREM2-KO mice and their littermate controls. However, in the sub-acute phase (7 d reperfusion following stroke, TREM2-KO mice showed a decreased transcription of pro-inflammatory cytokines TNFα, IL-1α and IL-1β, associated with a reduced microglial activity (CD68, Iba1. Furthermore, TREM2-KO mice showed a reduced transcription of chemokines CCL2 (MCP1, CCL3 (MIP1α and the chemokine receptor CX3CR1, followed by a diminished invasion of CD3-positive T-cells. No effect on the lesion size was observed. CONCLUSIONS: Although we initially expected an exaggerated pro-inflammatory response following ablation of TREM2, our data support a contradictory scenario that the sub-acute inflammatory reaction after stroke is attenuated in TREM2-KO mice. We therefore conclude that TREM2 appears to sustain a distinct inflammatory response after stroke.

  8. Attenuated Inflammatory Response in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Knock-Out Mice following Stroke

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    Brehm, Martin; Guenther, Madlen; Linnartz-Gerlach, Bettina; Neumann, Harald; Witte, Otto W.; Frahm, Christiane

    2013-01-01

    Background Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial surface receptor involved in phagocytosis. Clearance of apoptotic debris after stroke represents an important mechanism to re-attain tissue homeostasis and thereby ensure functional recovery. The role of TREM2 following stroke is currently unclear. Methods and Results As an experimental stroke model, the middle cerebral artery of mice was occluded for 30 minutes with a range of reperfusion times (duration of reperfusion: 6 h/12 h/24 h/2 d/7 d/28 d). Quantitative PCR (qPCR) revealed a greatly increased transcription of TREM2 after stroke. We subsequently analyzed the expression of pro-inflammatory cytokines, chemokines and their receptors in TREM2-knockout (TREM2-KO) mice via qPCR. Microglial activation (CD68, Iba1) and CD3-positive T-cell invasion were analyzed via qPCR and immunohistochemistry. Functional consequences of TREM2 knockout were assessed by infarct volumetry. The acute inflammatory response (12 h reperfusion) was very similar between TREM2-KO mice and their littermate controls. However, in the sub-acute phase (7 d reperfusion) following stroke, TREM2-KO mice showed a decreased transcription of pro-inflammatory cytokines TNFα, IL-1α and IL-1β, associated with a reduced microglial activity (CD68, Iba1). Furthermore, TREM2-KO mice showed a reduced transcription of chemokines CCL2 (MCP1), CCL3 (MIP1α) and the chemokine receptor CX3CR1, followed by a diminished invasion of CD3-positive T-cells. No effect on the lesion size was observed. Conclusions Although we initially expected an exaggerated pro-inflammatory response following ablation of TREM2, our data support a contradictory scenario that the sub-acute inflammatory reaction after stroke is attenuated in TREM2-KO mice. We therefore conclude that TREM2 appears to sustain a distinct inflammatory response after stroke. PMID:23301011

  9. Emissions from commercial-grade charbroiling meat operations induce oxidative stress and inflammatory responses in human bronchial epithelial cells

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    Ning Li

    2014-01-01

    Full Text Available Commercial charbroiling emissions are a significant source of ambient particulate matter (PM in urban settings. The objective of this study was to determine whether organic extract of PM emissions from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells and whether this effect was mediated by oxidative stress. PM samples were collected during cooking hamburgers on a commercial-grade under-fired charbroiler and sequentially extracted with water and methanol to obtain the aqueous PM suspension (AqPM and organic extract (OE. The pro-oxidative and pro-inflammatory effects of OE were assessed using human bronchial epithelial cell line BEAS-2B. While AqPM did not have any effect, OE effectively induced the expression of heme oxygennase-1 and cyclooxygenase-2 in BEAS-2B cells. OE also up-regulated the levels of IL-6, IL-8, and prostaglandin E2. OE-induced cellular inflammatory response could be effectively suppressed by the antioxidant N-acetyl cysteine, nuclear factor (erythroid-derived 2-like 2 activator sulforaphane and p38 MAPK inhibitor SB203580. In conclusion, organic chemicals emitted from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells, which was mediated by oxidative stress and p38 MAPK.

  10. Divergent responses to peptidoglycans derived from different E. coli serotypes influence inflammatory outcome in trout, Oncorhynchus mykiss, macrophages

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    Goetz Frederick

    2011-01-01

    Full Text Available Abstract Background Pathogen-associated molecular patterns (PAMPs are structural components of pathogens such as lipopolysaccharide (LPS and peptidoglycan (PGN from bacterial cell walls. PAMP-recognition by the host results in an induction of defence-related genes and often the generation of an inflammatory response. We evaluated both the transcriptomic and inflammatory response in trout (O. mykiss macrophages in primary cell culture stimulated with DAP-PGN (DAP; meso-diaminopimelic acid, PGN; peptidoglycan from two strains of Escherichia coli (PGN-K12 and PGN-O111:B4 over time. Results Transcript profiling was assessed using function-targeted cDNA microarray hybridisation (n = 36 and results show differential responses to both PGNs that are both time and treatment dependent. Wild type E. coli (K12 generated an increase in transcript number/diversity over time whereas PGN-O111:B4 stimulation resulted in a more specific and intense response. In line with this, Gene Ontology analysis (GO highlights a specific transcriptomic remodelling for PGN-O111:B4 whereas results obtained for PGN-K12 show a high similarity to a generalised inflammatory priming response where multiple functional classes are related to ribosome biogenesis or cellular metabolism. Prostaglandin release was induced by both PGNs and macrophages were significantly more sensitive to PGN-O111:B4 as suggested from microarray data. Conclusion Responses at the level of the transcriptome and the inflammatory outcome (prostaglandin synthesis highlight the different sensitivity of the macrophage to slight differences (serotype in peptidoglycan structure. Such divergent responses are likely to involve differential receptor sensitivity to ligands or indeed different receptor types. Such changes in biological response will likely reflect upon pathogenicity of certain serotypes and the development of disease.

  11. Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress.

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    Vecchiarelli, Haley A; Gandhi, Chaitanya P; Gray, J Megan; Morena, Maria; Hassan, Kowther I; Hill, Matthew N

    2016-01-01

    There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical-amygdala circuit in the regulation of the neurobehavioral responses to stress.

  12. Evaluation of host inflammatory responses of β-tricalcium phosphate bioceramics caused by calcium pyrophosphate impurity using a subcutaneous model.

    Science.gov (United States)

    Lin, Kaili; Yuan, Wei; Wang, Lu; Lu, Jianxi; Chen, Lei; Wang, Zhen; Chang, Jiang

    2011-11-01

    Implantation of synthetic materials into body elicits inflammatory host responses that limit medical device integration and biological performance. Since the effective use of biomaterials in vivo requires good biocompatibility and bio-functionality, it is vital that we assess the inflammatory reactions provoked by various implanted biomaterials. In chemical precipitation of β-tricalcium phosphate [β-Ca₃(PO₄)₂, β-TCP], the impurity of calcium pyrophosphate (Ca₂P₂O₇, CPP) will easily appear if the preparation conditions are not well controlled. To test the influences of CCP-impurity on the biocompatibility of the material, four groups of β-TCP ceramic samples doped with 0.5-10 wt % of CCP impurity, and pure β-TCP and CCP samples were fabricated and implanted in rat subcutaneous site for one, two, and four weeks. The host tissue responses to the ceramics were evaluated by histomorphometric analysis, and the results were compared with pure β-TCPbioceramics. The results show that the CPP impurity can elicit and stimulate the inflammatory responses at the tissue/implant interface. Moreover, with the increase of CPP doping amount, the inflammation increases apparently. However, the pure β-TCP bioceramics only present slight post-implantation inflammatory responses. The influence of the CPP doping on the inflammatory responses is mainly related to a microparticles release because of an insufficient sintering of β-TCP by CPP doping. The microparticle release could be at the origin of local inflammation and cell/tissue damages. Therefore, to obtain perfect biocompatibility and high quality β-TCP bioceramics, it is important to avoid and control the CPP impurity in the preparation of β-TCP powders and bioceramics.

  13. Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men

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    Volek Jeff S

    2008-02-01

    Full Text Available Abstract Background Carbohydrate restricted diets (CRD consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. Methods Twenty eight overweight men [body mass index (BMI 26–37 kg/m2] aged 40–70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26 for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15 (640 mg additional cholesterol/day provided by eggs or placebo (SUB, n = 13 (no additional dietary cholesterol. Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP, tumor necrosis factor-alpha (TNF-α, interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1(VCAM-1. Results Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P Conclusion A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.

  14. Polysaccharide extract of Mimosa tenuiflora stem barks stimulates acute inflammatory response via nitric oxide

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    Kaira Emanuella Sales da Silva-Leite

    2016-12-01

    Full Text Available Mimosa tenuiflora (Mimosaceae or “jurema-preta” is well distributed in the northeast Brazil, being popularly used to treat skin lesions, burns and inflammation. The healing effect of the alcoholic extract prepared with its barks corroborates the popular use. This study aimed to evaluate the inflammatory response of polysaccharides extracted from M. tenuiflora barks (EP-Mt by methanol/NaOH and ethanol precipitation. Inflammatory activity was assessed in rat models of acute inflammation (paw edema and peritonitis, by the following parameters: edema, vascular permeability, leukocyte migration, myeloperoxidase activity and pharmacological modulation of nitric oxide and prostaglandins. EP-Mt presented 3.8% yield, 41% carbohydrate and 0.34% protein. EP-Mt (0.01, 0.1, 1.0 mg kg-1 injected by subcutaneous route elicited paw edema that lasted from 30-420 min, with maximal effect at 1 mg kg-1 (40x vs. saline, and was inhibited by L-NAME (52% and dexamethasone (26%. EP-Mt (1 mg kg-1, via intraperitoneal stimulated leukocytes migration (2.2x, mainly neutrophils (6.5x and MPO activity (96%. The leukocyte migration elicited by EP-Mt was inhibited by dexamethasone (39% and L-NAME (38%. EP-Mt containing high carbohydrate content induces acute inflammation via nitric oxide, which open perspectives of application in pathological conditions of immunosuppression.

  15. Neuromuscular and inflammatory responses to handball small-sided games: the effects of physical contact.

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    Dello Iacono, A; Eliakim, A; Padulo, J; Laver, L; Ben-Zaken, S; Meckel, Y

    2016-09-30

    The aim of this study was to investigate the influence of physical contact on neuromuscular impairments and inflammatory response during handball small-sided games. Using a counterbalanced design, 12 elite male junior handball players were divided into two groups: contact (C-SSG) and no-contact (NC-SSG), performing both contact and no-contact small-sided games, in reverse order on two training sessions separated by 5 days. The methodology and rules were identical for the two SSG regimens, with the only difference being the inclusion or prohibition of upper body use for physical contacts. Upper and lower body neuromuscular performances and blood concentrations of inflammatory cytokine IL-6 were assessed before and immediately after the games. During small-sided games, video analysis was used to establish the physical contact counts. Significant differences were found in most upper and lower limbs muscles kinetic variables and in the physical contact events (all P handball players. These outcomes outline the specific physiological profile of C-SSG that, in turn, might be used by practitioners and coaches as a practical approach to strategically select exercises in athlete's overall training program.

  16. Mesenteric microvascular inflammatory responses to systemic hypoxia are mediated by PAF and LTB4.

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    Casillan, Alfred J; Gonzalez, Norberto C; Johnson, Jennifer S; Steiner, Dawn R S; Wood, John G

    2003-06-01

    Systemic hypoxia produces a rapid microvascular inflammatory response characterized by increased reactive oxygen species (ROS) levels, leukocyte-endothelial adherence and emigration, and increased vascular permeability. The lipid inflammatory mediator leukotriene B(4) (LTB(4)) is involved in the early hypoxia-induced responses (ROS generation and leukocyte adherence). Whether other lipid inflammatory mediators participate in this phenomenon is not known. The objective of these experiments was to study the role of platelet-activating factor (PAF) in the microvascular inflammatory response to hypoxia and its potential interactions with LTB(4) in this response. Intravital microscopy was used to examine mesenteric venules of anesthetized rats. We found that WEB-2086, a PAF receptor antagonist, completely prevented the increase in ROS levels and leukocyte adherence during a brief reduction in inspired Po(2) to anesthetized rats; administration of either WEB-2086 or the LTB(4) antagonist LTB(4)-DMA attenuated leukocyte emigration and the increase in vascular permeability to the same extent during prolonged systemic hypoxia in conscious rats. Furthermore, no additive effect was observed in either response when both antagonists were administered simultaneously. This study demonstrates a role for PAF in the rapid microvascular inflammatory response to hypoxia, as well as contributions of PAF and LTB(4) to the slowly developing responses observed during sustained hypoxia. The incomplete blockade of the hypoxia-induced increases in vascular permeability and leukocyte emigration by combined administration of both antagonists indicates that factors in addition to LTB(4) and PAF participate in these phenomena.

  17. Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide.

    Science.gov (United States)

    Frank, Matthew G; Miguel, Zurine D; Watkins, Linda R; Maier, Steven F

    2010-01-01

    Acute and chronic stress has been found to sensitize or prime the neuroinflammatory response to both peripheral and central immunologic challenges. Several studies suggest that stress-induced sensitization of neuroinflammatory processes may be mediated by the glucocorticoid (GC) response to stress. GCs, under some conditions, exhibit pro-inflammatory properties, however whether GCs are sufficient to prime neuroinflammatory responses has not been systematically investigated. In the present investigation, we tested whether acute administration of exogenous GCs would be sufficient to reproduce the stress-induced sensitization of neuroinflammatory responses under a number of different timing relationships between GC administration and immune challenge (lipopolysaccharide; LPS). We demonstrate here that GCs potentiate both the peripheral (liver) and central (hippocampus) pro-inflammatory response (e.g. TNFalpha, IL-1beta, IL-6) to a peripheral immune challenge (LPS) if GCs are administered prior (2 and 24h) to challenge. Prior exposure (24h) to GCs also potentiated the pro-inflammatory response of hippocampal microglia to LPS ex vivo. In contrast, when GCs are administered after (1h) a peripheral immune challenge, GCs suppress the pro-inflammatory response to LPS in both liver and hippocampus. GCs also up-regulated microglial activation markers including Toll-like Receptor 2. The present data suggest that the temporal relationship between GC treatment and immune challenge may be an important factor determining whether GCs exhibit pro- or anti-inflammatory properties.

  18. Topical insulin application improves healing by regulating the wound inflammatory response.

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    Chen, Xuelian; Liu, Yan; Zhang, Xiong

    2012-01-01

    Inflammation, the initiating stage of wound healing, is characterized by increased endothelial permeability, infiltration of inflammatory cells, and secretion of numerous growth factors and chemokines. By controlling wound contamination and infection, as well as inducing the repairing process, inflammatory response plays an irreplaceable role during wound healing. We utilized a variety of approaches to observe the effect of insulin on wound inflammatory response, specifically the effect of insulin on the function of wound macrophages. We also investigated whether insulin-regulated inflammatory response contributed to insulin-induced healing. Mice excisional wounds treated with insulin showed advanced infiltration and resolution of macrophages, which correlated with the expression of monocyte chemotactic protein-1, a potent chemotactic factor for macrophages. Blockage of monocyte chemotactic protein-1 resulted in reduced macrophages infiltration and impaired wound healing despite the presence of insulin. In vitro studies showed insulin-facilitated monocytes/macrophages chemotaxis, pinocytosis/phagocytosis, and secretion of inflammatory mediators as well. Our study strongly suggests that insulin is a potent healing accelerant. Regulating wound inflammatory response, especially the quantity and function of macrophages, is one of the mechanisms explaining insulin-induced accelerated wound healing.

  19. MicroRNA-155 in exosomes secreted from helicobacter pylori infection macrophages immunomodulates inflammatory response

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    Wang, Jianjun; Deng, Zhiyong; Wang, Zeyou; Wu, Jianhong; Gu, Tao; Jiang, Yibiao; Li, Guangxin

    2016-01-01

    Exosomes containing microRNA-155 act as molecule carriers during immune cell-cell communication and play an important role in the inflammatory response of H. pylori infection macrophages. Previous reports have found that miR-155 was over-expressed in H. pylori infection macrophages, but the significance of which is still unknown. In this study, we analyzed the impact of miR-155 loaded in exosomes derived from macrophages to the inflammatory response of H. pylori infection macrophages and possible mechanisms. We found that miR-155 promoted the expression of inflammatory cytokines including TNF-a, IL-6, IL-23, but also increased the expression of CD40, CD63, CD81, and MCH-I. Meanwhile, inflammatory signal pathways proteins, such as MyD88, NF-κB in H. pylori infection macrophages were down-regulated due to the over-expression of miR-155. Experiments in vitro or in vivo revealed that miR-155 promoted macrophages to inhibit or kill H. pylori by regulating the inflammatory response of cells to prevent the gastritis caused by H. pylori infection. These findings contribute to the understanding of miR-155 contained in exosomes in inflammatory responses of H. pylori infection macrophages. PMID:27725852

  20. Advances in the assessment of disease activity in inflammatory bowel disease

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    Camilleri, M.; Proano, M. (Mayo Clinic, Rochester, MN (USA))

    1989-07-01

    Knowledge of the severity and extent of the inflammation in inflammatory bowel diseases provides a means of determining rational therapeutic strategies in affected patients. During the past 3 decades, several clinical, laboratory, and combined indices have been proposed for the assessment of inflammatory bowel disease; refinements in radiologic methods and the availability of endoscopy and biopsy have facilitated the accurate assessment of the extent and severity of the disease. In relapsing conditions such as inflammatory bowel disease, however, the use of such procedures is limited by the radiation exposure or the relatively invasive nature of the technique. In this article, we review the proposed methods and recent advances in assessment of patients with inflammatory bowel disease; we also discuss possible strategies at the time of diagnosis, during recurrence, and in evaluation of the efficacy of drug or dietic therapy. 58 references.

  1. Weight cycling enhances adipose tissue inflammatory responses in male mice.

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    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  2. Sirt2 suppresses inflammatory responses in collagen-induced arthritis

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    Lin, Jiangtao [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Sun, Bing; Jiang, Chuanqiang; Hong, Huanyu [Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Zheng, Yanping, E-mail: yanpingzheng@yahoo.com [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)

    2013-11-29

    Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.

  3. Avaliação da aprotinina na redução da resposta inflamatória sistêmica em crianças operadas com circulação extracorpórea Assessment of aprotinin in the reduction of inflammatory systemic response in children undergoing surgery with cardiopulmonary bypass

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    Cesar Augusto Ferreira

    2010-03-01

    Full Text Available OBJETIVO: Avaliar se a aprotinina em altas doses hemostáticas pode reduzir o processo inflamatório após circulação extracorpórea (CEC em crianças. MÉTODOS: Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9 e o outro, Aprotinina (n=10. Neste, o fármaco foi administrado antes e durante a CEC. A resposta inflamatória sistêmica e disfunções hemostática e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com POBJECTIVE: To assess if the hemostatic high-dose aprotinin is able to reduce the inflammatory process after cardiopulmonary bypass (CPB in children. METHODS: A prospective randomized study was performed on children aged 30 days to 4 years who underwent correction of acyanogenic congenital heart disease with CPB and were divided into two groups: Control (n=9 and Aprotinin (n=10. In the Aprotinin Group the drug was administered before and during CPB and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were assessed through clinical and biochemical markers. Differences were considered to be significant when P<0.05. RESULTS: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, staying in the postoperative ICU and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/ inspired oxygen fraction ratio (PaO2/FiO2 was significantly reduced 24 h after surgery in the Control Group. Blood loss was similar for both groups. Significant leukopenia was observed in the Aprotinin Group during CPB, followed by leukocytosis. Tumor necrosis factor alpha (TNF- α, interleukins (IL

  4. African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

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    Benoit Stijlemans

    2017-05-01

    Full Text Available African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i early parasite diagnosis, (ii anti-trypanosome (drugs treatment, and (iii anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination.

  5. The effect of brain injury on the inflammatory response following severe trauma.

    Science.gov (United States)

    Lustenberger, T; Kern, M; Relja, B; Wutzler, S; Störmann, P; Marzi, I

    2016-03-01

    The inflammatory response is an important part of the pathophysiology of severe injury and, in particular, of severe traumatic brain injury (TBI). This study evaluates the inflammatory course following major trauma and focuses on the effect of severe TBI on inflammatory markers. This was a retrospective analysis of prospectively collected data in 123 severely injured (ISS ≥16) trauma patients. The study cohort was divided into patients with isolated TBI (Head AIS ≥3, all other AIS trauma. Significant correlations between admission IL-6 values and the development of MOF, sepsis and the neurological outcome were found in patients with TBI. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Investigation of centrally and peripherally acting analgesic and anti inflammatory activity of biological immune response modulator (an Amazonian plant extract) in animal models of pain and inflammation

    OpenAIRE

    Mital Ravalji; Edwin Cevallos-Arellano; Suresh Balakrishnan

    2015-01-01

    Background: Biological immune response modulator (BIRM) - An aqueous extract of dried roots of the species Dulcamara (family Solanaceae) grown in Ecuador, considered as a natural remedy for various disease is promoted as a natural herbal medicine. Our aim of the study was to assess the central and peripheral analgesic and anti-inflammatory property of BIRM and to study its mechanism of action. Methods: Peripheral analgesic and anti-inflammatory activity was evaluated using acetic acid indu...

  7. Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical benefits of pelotherapy in osteoarthritis patients: regulation of the altered inflammatory and stress feedback response

    Science.gov (United States)

    Ortega, E.; Gálvez, I.; Hinchado, M. D.; Guerrero, J.; Martín-Cordero, L.; Torres-Piles, S.

    2017-04-01

    The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis (OA) patients. This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre `El Raposo' (Spain) in a group of 21 OA patients diagnosed with primary knee OA. Clinical assessments included pain intensity using a visual analog scale; pain, stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index; and health-related quality of life using the EuroQol-5D questionnaire. Serum inflammatory cytokine levels (IL-1β, TNF-α, IL-8, IL-6, IL-10 and TGF-β) were evaluated using the Bio-Plex® Luminex® system. Circulating neuroendocrine-stress biomarkers, such as cortisol and extracellular 72 kDa heat shock protein (eHsp72), were measured by ELISA. After the cycle of mud therapy, OA patients improved the knee flexion angle and OA-related pain, stiffness and physical function, and they reported a better health-related quality of life. Serum concentrations of IL-1β, TNF-α, IL-8, IL-6 and TGF-β, as well as eHsp72, were markedly decreased. Besides, systemic levels of cortisol increased significantly. These results confirm that the clinical benefits of mud therapy may well be mediated, at least in part, by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients. Thus, mud therapy could be an effective alternative treatment in the management of OA.

  8. Effect of ketoprofen treatment on the uterine inflammatory response after AI of jennies with frozen semen.

    Science.gov (United States)

    Vilés, K; Rabanal, R; Rodríguez-Prado, M; Miró, J

    2013-04-15

    Artificial insemination (AI) involving the placing of frozen-thawed semen directly into the jenny uterine body is associated with very low pregnancy rates. This might be because of an exacerbation of the acute response of the endometrium to sperm, as seen in mares with persistent induced mating endometritis. Pregnancy rates can be increased in such mares, however, by including anti-inflammatory treatments in the insemination protocol (Bucca S, Carli A, Buckley T, Dolci G, Fogarty U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis. Theriogenology 2008;70:1093-100; Rojer H, Aurich C. Treatment of persistent mating-induced endometritis in mares with the non-steroid anti-inflammatory drug vedaprofen. Reprod Domest Anim 2010;45:e458-60). To investigate the endometritis caused by the use of frozen-thawed semen in jennies, and to assess the response to ketoprofen treatment, endometrial cytological samples and biopsies from six healthy jennies were examined in a crossover design experiment. Samples were taken from jennies in estrus (E; control) and at 6 hours after AI with or without ketoprofen (+K and -K, respectively). Ketoprofen was administered iv 24 hours before and for 4 days after insemination (total = 2.2 mg/kg/24 hours for 5 days). All animals showed a severe inflammatory response to semen deposition. Polymorphonuclear neutrophil numbers in the cytological smears and biopsies differed significantly between the +K and E animals. No significant differences were recorded, however, between the +K and -K treatments. Eosinophils were observed in all sample types from all groups; these cells appear to be a feature of the normal jenny endometrium. Slight fibrosis was observed in some biopsies, but no significant relationship with inflammation was found. Intense cyclooxygenase-2 (COX-2) immunohistochemical labeling was detected in the -K biopsies. Less intense labeling was seen in those of the +K

  9. 20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

    OpenAIRE

    Landis, R. Clive

    2015-01-01

    The “systemic inflammatory response” has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis ...

  10. Spontaneous one-lung ventilation increases the lung inflammatory response : an experimental pilot study

    OpenAIRE

    Machado, Humberto S; Sá, Paula; Nunes, Catarina S; Couceiro, António; Silva, Álvaro Moreira da; Águas, Artur

    2014-01-01

    Study objective: The purpose of this study was to investigate if spontaneous one-lung ventilation would induce any type of inflammatory lung response when compared to spontaneous two-lung ventilation and its intensity, by quantification of inflammatory cells in lung histology at the end of the procedure. Design: In vivo prospective randomised animal study Setting: University research laboratory Subjects: New Zealand rabbits Interventions: Rabbits (n=20) were randomly assigned to 4 groups (n=5...

  11. Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats.

    Science.gov (United States)

    Wang, Qian-Qian; Zhu, Li-Jun; Wang, Xian-Hong; Zuo, Jian; He, Hui-Yan; Tian, Miao-Miao; Wang, Lei; Liang, Gui-Ling; Wang, Yu

    2016-05-01

    Trigeminal nerve stimulation (TNS) has recently been demonstrated effective in the treatment of epilepsy and mood disorders. Here, we aim to determine the effects of TNS on epileptogenesis, cognitive function, and the associated hippocampal apoptosis and inflammatory responses. Rats were injected with pilocarpine to produce status epilepticus (SE) and the following chronic epilepsy. After SE induction, TNS treatment was conducted for 4 consecutive weeks. A pilocarpine re-injection was then used to induce a seizure in the epileptic rats. The hippocampal neuronal apoptosis induced by seizure was assessed by TUNEL staining and inflammatory responses by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). The spontaneous recurrent seizure (SRS) number was counted through video monitoring, and the cognitive function assessed through Morris Water Maze (MWM) test. TNS treatment attenuated the SRS attacks and improved the cognitive impairment in epileptic rats. A pilocarpine re-injection resulted in less hippocampal neuronal apoptosis and reduced level of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and microglial activation in epileptic rats with TNS treatment in comparison to the epileptic rats without TNS treatment. It is concluded that TNS treatment shortly after SE not only protected against the chronic spontaneous seizures but also improved cognitive impairments. These antiepileptic properties of TNS may be related to its attenuating effects on hippocampal apoptosis and pro-inflammatory responses.

  12. Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study

    Science.gov (United States)

    Parenica, Jiri; Jarkovsky, Jiri; Malaska, Jan; Mebazaa, Alexandre; Gottwaldova, Jana; Helanova, Katerina; Litzman, Jiri; Dastych, Milan; Tomandl, Josef; Spinar, Jindrich; Dostalova, Ludmila; Lokaj, Petr; Tomandlova, Marie; Pavkova, Monika Goldergova; Sevcik, Pavel; Legrand, Matthieu

    2017-01-01

    ABSTRACT Introduction: Patients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers. Methods: Eighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock. Results: Infection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875. Conclusion: The prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most

  13. Balance Between the Proinflammatory and Anti-Inflammatory Immune Responses with Blood Transfusion in Sepsis.

    Science.gov (United States)

    Rice, Teresa C; Pugh, Amanda M; Caldwell, Charles C; Schneider, Barbara St Pierre

    2017-09-01

    Blood product transfusion may exacerbate the initial immunosuppressive response of sepsis. Nurses and other patient care providers must be diligent in recognizing and managing a worsening immune status, using flow cytometry to monitor patients' immune status. This type of monitoring may be instrumental in reducing morbidity and mortality in persons with sepsis. This article discusses the recent literature on the associated inflammatory responses that occur with blood transfusion and provides an analysis of alterations in key inflammatory pathways in response to transfusion in a sepsis population. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Thymosin Beta-4 Suppresses Osteoclastic Differentiation and Inflammatory Responses in Human Periodontal Ligament Cells.

    Directory of Open Access Journals (Sweden)

    Sang-Im Lee

    Full Text Available Recent reports suggest that thymosin beta-4 (Tβ4 is a key regulator for wound healing and anti-inflammation. However, the role of Tβ4 in osteoclast differentiation remains unclear.The purpose of this study was to evaluate Tβ4 expression in H2O2-stimulated human periodontal ligament cells (PDLCs, the effects of Tβ4 activation on inflammatory response in PDLCs and osteoclastic differentiation in mouse bone marrow-derived macrophages (BMMs, and identify the underlying mechanism.Reverse transcription-polymerase chain reactions and Western blot analyses were used to measure mRNA and protein levels, respectively. Osteoclastic differentiation was assessed in mouse bone marrow-derived macrophages (BMMs using conditioned medium (CM from H2O2-treated PDLCs.Tβ4 was down-regulated in H2O2-exposed PDLCs in dose- and time-dependent manners. Tβ4 activation with a Tβ4 peptide attenuated the H2O2-induced production of NO and PGE2 and up-regulated iNOS, COX-2, and osteoclastogenic cytokines (TNF-α, IL-1β, IL-6, IL-8, and IL-17 as well as reversed the effect on RANKL and OPG in PDLCs. Tβ4 peptide inhibited the effects of H2O2 on the activation of ERK and JNK MAPK, and NF-κB in PDLCs. Furthermore, Tβ4 peptide inhibited osteoclast differentiation, osteoclast-specific gene expression, and p38, ERK, and JNK phosphorylation and NF-κB activation in RANKL-stimulated BMMs. In addition, H2O2 up-regulated Wnt5a and its cell surface receptors, Frizzled and Ror2 in PDLCs. Wnt5a inhibition by Wnt5a siRNA enhanced the effects of Tβ4 on H2O2-mediated induction of pro-inflammatory cytokines and osteoclastogenic cytokines as well as helping osteoclastic differentiation whereas Wnt5a activation by Wnt5a peptide reversed it.In conclusion, this study demonstrated, for the first time, that Tβ4 was down-regulated in ROS-stimulated PDLCs as well as Tβ4 activation exhibited anti-inflammatory effects and anti-osteoclastogenesis in vitro. Thus, Tβ4 activation might be a

  15. Role of inflammatory cytokines in the response of solid cancers to photodynamic therapy

    Science.gov (United States)

    Korbelik, Mladen; Sun, Jinghai; Cecic, Ivana; Dougherty, Graeme J.

    2001-04-01

    Photodynamic therapy (PDT) elicits a strong acute inflammatory response that has both local and systemic (acute phase response) attributes. The insult mediated by PDT-induced oxidative stress at the targeted site triggers a complex multifactorial response engaging host defence mechanisms associated with the inflammatory process to participate in the eradication of the treated tumor. Inflammatory cytokines are important mediators of critical events in this process as they regulate the activity of inflammatory, endothelial and other cells. The initial stimulus for enhanced production and release of cytokines likely originates from several types of events, such as activated transcription factors and complement deposition. The PDT-induced complement activation appears to be directly linked to the enhanced expression of various cytokines, including chemokines such as KC (in mouse models), and classic inflammatory cytokines such as IL-1β, TNF-α , IL-6 and IL-10. A variety of interventions that modulate the activity of particular cytokines performed in conjunction with PDT were shown to influence the therapy outcome. The treatments such as using blocking antibodies and local or systemic cytokine delivery may either reduce or dramatically improve the curative effect of PDT. The inflammatory and related cytokines that at present appear particularly interesting and merit further investigation for use as adjuvants to PDT are IL-3, IL-8, IL-15, TNF-α, IFN-γ, G-CSF and GM-CSF.

  16. Potential use of salivary markers for longitudinal monitoring of inflammatory immune responses to vaccination

    NARCIS (Netherlands)

    Lim, Pei Wen; Garssen, Johan; Sandalova, Elena

    2016-01-01

    Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies larg

  17. Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection

    NARCIS (Netherlands)

    Davis, C.J.; Zielinski, M.R.; Dunbrasky, D.; Taishi, P.; Dinarello, C.A.; Krueger, J.M.

    2017-01-01

    Multiple interactions between the immune system and sleep are known, including the effects of microbial challenge on sleep or the effects of sleep loss on facets of the immune response. Cytokines regulate, in part, sleep and immune responses. Here we examine the role of an anti-inflammatory

  18. Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response.

    Science.gov (United States)

    Li, Chang Xian; Lo, Chung Mau; Lian, Qizhou; Ng, Kevin Tak-Pan; Liu, Xiao Bing; Ma, Yuen Yuen; Qi, Xiang; Yeung, Oscar Wai Ho; Tergaonkar, Vinay; Yang, Xin Xiang; Liu, Hui; Liu, Jiang; Shao, Yan; Man, Kwan

    2016-05-10

    Repressor and activator protein (Rap1) directly regulates nuclear factor-κB (NF-κB) dependent signaling, which contributes to hepatic IRI. We here intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying mechanisms. The association of Rap1 expression with hepatic inflammatory response were investigated in both human and rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1 knockout mice IRI model in vivo and primary cells in vitro. Our results showed that over expression of Rap1 was associated with severe liver graft inflammatory response, especially in living donor liver transplantation. The results were also validated in rat liver transplantation model. In mice hepatic IRI model, the knockout of Rap1 reduced hepatic damage and hepatic inflammatory response. In primary cells, the knockout of Rap1 suppressed neutrophils migration activity and adhesion in response to liver sinusoidal endothelial cells through down-regulating neutrophils F-Actin expression and CXCL2/CXCR2 pathway. In addition, the knockout of Rap1 also decreased production of pro-inflammatory cytokines/chemokines in primary neutrophils and neutrophils-induced hepatocyte damage. In conclusion, Rap1 may induce hepatic IRI through promoting neutrophils inflammatory response. Rap1 may be the potential therapeutic target of attenuating hepatic IRI.

  19. Impact of nutrition on immune function and the inflammatory response

    Science.gov (United States)

    The review utilizes data on three micronutrients (vitamin A, zinc and iron), anthropometrically defined undernutrition (stunting, wasting and underweight) and obesity to evaluate the effect on immune function, recovery of immune function in response to nutritional interventions, related health outco...

  20. Betahistine attenuates murine collagen-induced arthritis by suppressing both inflammatory and Th17 cell responses.

    Science.gov (United States)

    Tang, Kuo-Tung; Chao, Ya-Hsuan; Chen, Der-Yuan; Lim, Yun-Ping; Chen, Yi-Ming; Li, Yi-Rong; Yang, Deng-Ho; Lin, Chi-Chen

    2016-10-01

    The objective of this study was to evaluate the potential therapeutic effects of betahistine dihydrochloride (betahistine) in a collagen-induced arthritis (CIA) mouse model. CIA was induced in DBA/1 male mice by primary immunization with 100μl of emulsion containing 2mg/ml chicken type II collagen (CII) mixed with complete Freund's adjuvant (CFA) in an 1:1 ratio, and booster immunization with 100μl of emulsion containing 2mg/ml CII mixed with incomplete Freund's adjuvant (IFA) in an 1:1 ratio. Immunization was performed subcutaneously at the base of the tail. After being boosted on day 21, betahistine (1 and 5mg/kg) was orally administered daily for 2weeks. The severity of CIA was determined by arthritic scores and assessment of histopathological joint destruction. Expression of cytokines in the paw and anti-CII antibodies in the serum was evaluated by ELISA. The proliferative response against CII in the lymph node cells was measured by (3)H-thymidine incorporation assay. The frequencies of different CII specific CD4(+) T cell subsets in the lymph node were determined by flow-cytometric analysis. Betahistine treatment attenuated the severity of arthritis and reduced the levels of pro-inflammatory cytokines, including TNF-α, IL-6, IL-23 and IL-17A, in the paw tissues of CIA mice. Lymph node cells from betahistine-treated mice showed a decrease in proliferation, as well as a lower frequency of Th17 cells. In vitro, betahistine suppressed CD4(+) T cell differentiation into Th17 cells. These results indicate that betahistine is effective in suppressing both inflammatory and Th17 responses in mouse CIA and that it may have therapeutic value as an adjunct treatment for rheumatoid arthritis.

  1. Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses.

    Science.gov (United States)

    Iwabuchi, Kazuhisa

    2015-01-01

    Glycosphingolipids (GSLs) are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. GSLs cluster with cholesterol in cell membranes to form GSL-enriched lipid rafts. Biochemical analyses have demonstrated that GSL-enriched lipid rafts contain several kinds of transducer molecules, including Src family kinases. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, is highly expressed on the plasma membranes of human phagocytes, and forms lipid rafts containing the Src family tyrosine kinase Lyn. LacCer-enriched lipid rafts mediate immunological and inflammatory reactions, including superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. LacCer also serves as a signal transduction molecule for functions mediated by CD11b/CD18-integrin (αM/β2-integrin, CR3, Mac-1), as well as being associated with several key cellular processes. LacCer recruits PCKα/ε and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and their adhesion to endothelial cells, as well as regulating β1-integrin clustering and endocytosis on cell surfaces. This review describes the organizational and inflammation-related functions of LacCer-enriched lipid rafts.

  2. Rosmarinus officinalis extract suppresses Propionibacterium acnes-induced inflammatory responses.

    Science.gov (United States)

    Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu; Tsai, Po-Jung

    2013-04-01

    Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes-induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes-stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes-induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes-induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes-induced inflammation.

  3. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study.

    Science.gov (United States)

    Lee, Trevor W R; Kowalski, Stephen; Falk, Kelsey; Maguire, Doug; Freed, Darren H; HayGlass, Kent T

    2016-01-01

    Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery. This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers. The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005). This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia. ClinicalTrials.gov NCT00348920.

  4. Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

    Directory of Open Access Journals (Sweden)

    Elster Eric A

    2010-05-01

    Full Text Available Abstract Background Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38% had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%. Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1, and MIP-2α (CXCL2. Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators. Conclusion These findings suggest that the

  5. TLR9 Activation Dampens the Early Inflammatory Response to Paracoccidioides brasiliensis, Impacting Host Survival

    Science.gov (United States)

    Menino, João Filipe; Saraiva, Margarida; Gomes-Alves, Ana G.; Lobo-Silva, Diogo; Sturme, Mark; Gomes-Rezende, Jéssica; Saraiva, Ana Laura; Goldman, Gustavo H.; Cunha, Cristina; Carvalho, Agostinho; Romani, Luigina; Pedrosa, Jorge; Castro, António Gil; Rodrigues, Fernando

    2013-01-01

    Background Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear. Methodology/Principal findings We used in vitro and in vivo models of infection by P. brasiliensis, comparing wild type and TLR9 deficient (−/−) mice, to assess the contribution of TLR9 on cytokine induction, phagocytosis and outcome of infection. We show that TLR9 recognizes either the yeast form or DNA from P. brasiliensis by stimulating the expression/production of pro-inflammatory cytokines by bone marrow derived macrophages, also increasing their phagocytic ability. We further show that TLR9 plays a protective role early after intravenous infection with P. brasiliensis, as infected TLR9−/− mice died at higher rate during the first 48 hours post infection than wild type mice. Moreover, TLR9−/− mice presented tissue damage and increased expression of several cytokines, such as TNF-α and IL-6. The increased pattern of cytokine expression was also observed during intraperitoneal infection of TLR9−/− mice, with enhanced recruitment of neutrophils. The phenotype of TLR9−/− hosts observed during the early stages of P. brasiliensis infection was reverted upon a transient, 48 hours post-infection, neutrophil depletion. Conclusions/Significance Our results suggest that TLR9 activation plays an early protective role against P. brasiliensis, by avoiding a deregulated type of inflammatory response associated to neutrophils that may lead to tissue damage. Thus

  6. Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria.

    Directory of Open Access Journals (Sweden)

    Marian Kacerovsky

    Full Text Available OBJECTIVE: This study aimed to evaluate the amniotic fluid protein profiles and the intensity of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria, using the multiplex xMAP technology. METHODS: A retrospective cohort study was undertaken in the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Czech Republic. A total of 145 pregnant women with preterm prelabor rupture of membranes between gestational age 24+0 and 36+6 weeks were included in the study. Amniocenteses were performed. The presence of Ureaplasma spp. and other bacteria was evaluated using 16S rRNA gene sequencing. The levels of specific proteins were determined using multiplex xMAP technology. RESULTS: The presence of Ureaplasma spp. and other bacteria in the amniotic fluid was associated with increased levels of interleukin (IL-6, IL-8, IL-10, brain-derived neurotropic factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and matrix metalloproteinasis-9. Ureaplasma spp. were also associated with increased levels of neurotropin-3 and triggering receptor expressed on myeloid cells-1. CONCLUSIONS: The presence of Ureaplasma spp. in the amniotic fluid is associated with a slightly different protein profile of inflammatory response, but the intensity of inflammatory response to Ureaplasma spp. is comparable with the inflammatory response to other bacteria.

  7. Metabolic factors-triggered inflammatory response drives antidepressant effects of exercise in CUMS rats.

    Science.gov (United States)

    Liu, Weina; Wang, Hongmei; Wang, Yangkai; Li, Haipeng; Ji, Liu

    2015-08-30

    Chronic stress is a potential contributing factor for depression, accompanying with metabolic and inflammatory response. Exercise is considered as a treatment for depression, but mechanisms underlying its beneficial effects still remain unknown. The objectives of present study were to confirm that metabolic factors-triggered inflammatory response mediates the antidepressant actions of exercise in chronic unpredictable mild stress (CUMS) rats. It has been found that CUMS stimulated expression of ghrelin and its receptor Ghsr, but inhibited expression of leptin and its receptor LepRb. Ghrelin, via binding to Ghsr, induced phosphorylation of GSK-3β on Tyr216 and decreased phosphorylation on Ser9, thus increasing GSK-3β activity. Conversely, ghrelin binding to Ghsr decreased STAT3 activity, through decreasing phosphorylation of STAT3 on Tyr705 and increasing Ser727 phosphorylation. Negatively correlated with ghrelin, leptin binding to LepRb had opposite effects on the activity of GSK-3β and STAT3 via phosphorylation. In addition, decreased leptin level initiated NLRP3 activity via LepRb. Furthermore, GSK-3β inhibited STAT3 activation, thus promoting the expression of NLRP3. Meanwhile, swim improved metabolic and inflammatory response both in CUMS and control rats. Our findings suggest that exercise not only ameliorates metabolic disturbance and inflammatory response in depression, but also contributes to metabolic and inflammatory function in normal conditions.

  8. An Update on the Inflammatory Response after Endovascular Repair for Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Eleni Arnaoutoglou

    2015-01-01

    Full Text Available Postimplantation syndrome (PIS is the clinical and biochemical expression of an inflammatory response following endovascular repair of an aortic aneurysm (EVAR. The goal of this review is to provide an update on the inflammatory response after endovascular repair of abdominal aortic aneurysm, discussing its causes and effects on the clinical outcome of the patient. PIS concerns nearly one-third of patients after EVAR. It is generally a benign condition, although in some patients it may negatively affect outcome. The different definitions and conclusions drawn from several studies reveal that PIS needs to be redefined with standardized diagnostic criteria. The type of the endograft’s material seems to play a role in the inflammatory response. Future studies should focus on a better understanding of the underlying pathophysiology, predictors, and risk factors as well as determining whether effective preventive strategies are necessary.

  9. CO liberated from CORM-2 modulates the inflammatory response in the liver of thermally injured mice

    Institute of Scientific and Technical Information of China (English)

    Bing-Wei Sun; Yan Sun; Zhi-Wei Sun; Xi Chen

    2008-01-01

    AIM: To explore the effects of CO-releasing molecules [tricarbonyldichlororuthenium (Ⅱ) dimer, CORM-2]-liberated CO on attenuation of inflammatory responses in liver of an experimental animal model of thermal injury and to investigate the associated potential mechanisms.METHODS: Thirty-six mice were assigned to three groups in three respective experiments. In each experiment, mice in sham group (n = 4) received sham thermal injury, whereas mice in burn group (n = 4) received a 15% of total body surface area (TBSA) full-thickness thermal injury, and mice in burn + CORM-2 group (n = 4) received the same thermal injury with immediate administration of CORM-2 (8 mg/kg, iv). Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. Levels of aminotransferases (ALT and AST) and nitric oxide (NO) were measured by biochemical methods. Tumor necrosis factor-α (TNF-α) and interleukin (IL-1β) activity, and the protein expression of iNOS and HO-1 in serum and tissue homogenates were assessed. In in vitro experiments, Kupffer cells were stimulated with LPS (10 μg/mL) for 4 h in the presence or absence of CORM-2 (10-100 μmol/L). Subsequently, the expression levels of TNF-α and NO production were assessed.RESULTS: Pro-inflammatory mediators (TNF-α, IL-1β, NO) in serum and liver homogenates of thermally injured mice were significantly reduced by CORM-2 administration. This was accompanied by a decrease in the expression of iNOS while an increase in the expression of HO-1 in the liver tissue. In parallel, the concentrations of TNF-α and NO in supernatants of LPS-stimulated Kupffer cells co-incubated with CORM-2 (10-100 μmol/L) were also markedly decreased.Histological examination demonstrated that CORM-2 could attenuate the leukocytes infiltration to the liver tissue.CONCLUSION: CORM-released CO modulates liver inflammation and significantly protects liver injury in burn mice by inhibiting the expression of iNOS and NO

  10. The inflammatory response in COPD : in mice and men

    NARCIS (Netherlands)

    Brandsma, Corry Anke

    2008-01-01

    The aim of this thesis was to investigate both the early and late effects of cigarette smoke and nitrogen dioxide (NO2) exposure and the potential dampening effects of heme oxygenase-1 (HO-1) in animal models for COPD. Additionally, we investigated the role of the specific immune response in the inf

  11. Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues.

    Science.gov (United States)

    Fry, Donald E

    2012-01-01

    Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.

  12. The Cutaneous Assessment Tool : development and reliability in juvenile idiopathic inflammatory myopathy

    NARCIS (Netherlands)

    Huber, A. M.; Dugan, E. M.; Lachenbruch, P. A.; Feldman, B. M.; Perez, M. D.; Zemel, L. S.; Lindsley, C. B.; Rennebohm, R. M.; Wallace, C. A.; Passo, M. H.; Reed, A. M.; Bowyer, S. L.; Ballinger, S. H.; Miller, F. W.; Rider, L. G.

    2007-01-01

    Objectives. Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater r

  13. VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells

    Science.gov (United States)

    Fraccaroli, Laura; Alfieri, Julio; Larocca, Luciana; Calafat, Mario; Roca, Valeria; Lombardi, Eduardo; Ramhorst, Rosanna; Leirós, Claudia Pérez

    2009-01-01

    Background and purpose Successful embryo implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects and promotes tolerogenic/Th2 responses while favouring embryonic development. We investigated the potential regulatory role of VIP on human trophoblast cells, maternal pro-inflammatory responses and trophoblast-maternal leukocyte interactions. Experimental approach We tested VIP effects directly on a trophoblast cell line (Swan 71 cells) and after co-culture with maternal peripheral blood mononuclear cells (PBMCs) as models of the feto-maternal dialogue. We also co-cultured maternal and paternal PBMCs to test effects of endogenous VIP on maternal alloresponses. Key results Swan 71 cells express VPAC1 receptors and VIP induced their proliferation and the expression of leukaemia inhibitor factor, a pro-implantatory marker. After interaction with trophoblast cells, VIP increased Foxp3, the proportion of CD4+CD25+Foxp3+ cells within maternal PBMCs and transforming growth factor β expression. Also, during the trophoblast-maternal PBMCs interaction, VIP reduced pro-inflammatory mediators [interleukin (IL)-6, monocyte chemoattractant protein 1, nitric oxide], while increasing IL-10. Trophoblast cells produced VIP which dose-dependently suppressed allomaternal responses, accompanied by reduced expression of the T cell transcription factor, T-bet. Conclusions and implications Vasoactive intestinal peptide induced pro-implantatory markers and trophoblast cell proliferation, while controlling the initial pro-inflammatory response, by increasing maternal regulatory T cells and anti-inflammatory cytokines. As an autocrine regulatory peptide VIP might contribute to fetal survival through two mechanisms; a direct trophic effect on trophoblast cells and an immunomodulatory effect that favours tolerance to fetal antigens. PMID:19133995

  14. Regulation of Toll-like receptors-dependent inflammatory response 

    Directory of Open Access Journals (Sweden)

    Ewa Kowalczyk

    2013-03-01

    Full Text Available Toll-like receptors (TLRs are a pivotal part of our innate immune response. They recognize a wide variety of pathogens and instigate an immune response, thus facilitating the removal of the disease-causing agent. Due to the intense nature of this response its strict control is of keyimportance, as a prolonged inflammatory signal leads to carcinogenesis and autoimmune disorders. The signaling cascade initiated by the activated TLR is complex and consists of multiple stages. It involves a variety of adaptor proteins, protein kinases and effector transcription factors. The number of stages in this process enables many possible checkpoints and ways of regulation. Signal modulation involves differentiated expression of TLRs, splicing variants of their adaptorproteins, enzymes modifying proteins engaged in the cascade and many more. This review focuses on endogenous factors responsible for controlling the TLR-dependent inflammatory response as well as on pharmacological therapies designed for regulating the innate immune response.  

  15. Uric acid promotes an acute inflammatory response to sterile cell death in mice

    Science.gov (United States)

    Kono, Hajime; Chen, Chun-Jen; Ontiveros, Fernando; Rock, Kenneth L.

    2010-01-01

    Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death–induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death–induced inflammatory responses in vivo. PMID:20501947

  16. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J;

    1999-01-01

    Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

  17. Immune-Manipulation of the Inflammatory Response in Acute Pancreatitis. What Can Be Expected?

    Directory of Open Access Journals (Sweden)

    Corinaldesi R

    2004-05-01

    Full Text Available Severe acute pancreatitis still has a high mortality rate and multiple organ failure is considered to be a severe complication of the disease. Activated polymorphonuclear leukocytes have an important role in the development of multiple organ failure which may result from acute pancreatitis and they are an important pathogenetic factor in the severity of this disease. Therefore, a logical therapeutic approach is to limit the organ damage by selective suppression of inflammatory mediators involved in the systemic inflammatory response syndrome and protect against systemic complication. In this paper, we review the recent literature data on the possible manipulation of the immune response in acute pancreatitis.

  18. A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response

    Science.gov (United States)

    Nash, Evelyn E.; Peters, Brian M.; Lilly, Elizabeth A.; Noverr, Mairi C.; Fidel, Paul L.

    2016-01-01

    Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC), particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata-associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans). Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN) recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1β, S100A8 alarmin, lactate dehydrogenase (LDH), and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1β, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co-infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation. PMID:26807975

  19. A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response.

    Directory of Open Access Journals (Sweden)

    Evelyn E Nash

    Full Text Available Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC, particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata-associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans. Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1β, S100A8 alarmin, lactate dehydrogenase (LDH, and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1β, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co-infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation.

  20. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    Science.gov (United States)

    2011-09-01

    the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression PRINCIPAL INVESTIGATOR: Paula J. McKeown-Longo, Ph.D...2011 4. TITLE AND SUBTITLE Fibronectin Matrix Remodeling in the Regulation of the 5a. CONTRACT NUMBER W81XWH-10-1-0755 Inflammatory Response within...hypothesis that force dependent unfolding of fibronectin in the tumor stroma drives an inflammatory response within the lung tumor microenvironment

  1. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    Science.gov (United States)

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-01-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c. Methods HbA1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  2. Assessment of analgesic and anti-inflammatory properties of crude extracts of ray fish, Narcine brunnea

    Institute of Scientific and Technical Information of China (English)

    Ravitchandirane V; Yogamoorthi A; Thangaraj M

    2012-01-01

    Objective: To assess the analgesic and anti-inflammatory properties of the crude petroleum ether and ether extracts of Narcine brunnea. Methods: The homogenized flesh was extracted exhaustively in a soxhlet apparatus separately with petroleum ether and ether. The Chemical analysis of petroleum ether and ether extracts was carried out by UV-VIS spectrophotometer, FT-IR and GC-MS. The analgesic and anti-inflammatory properties of the crude extract was assessed by hot plate, Haffner’s tail clip and carrageenan induced rat paw oedema methods in animal models. Results: The GC-MS and EIMS revealed five compounds viz. 3, 5- dihydroxy phenyl acetic acid, phtha1ic acid, N-methyl 2, 3-dihydro 3-but-2-enyl indole 5-sulphonic acid, 2-methoxy serotonin sulphate and 3-but-2 enyl-indole-5- sulphonic acid. The results (mean±SE) of hot plate showed that the crude petroleum ether and ether extracts exhibited increase in basal reaction time from 2.150±0.043 and 2.300±0.058 at 0 min to 6.102±0.037 and 8.783±0.070 at 120 min respectively. The tail clip method revealed a well marked increase in basal reaction time of 6.817±0.031 in petroleum ether and 8.852±0.043 in ether extract at 120 min. The crude petroleum ether inhibited the oedema volume of 51% with a mean oedema volume of 3.465±0.022 at 4h, where as the crude ether extract produced to the extent of 56% inhibition of oedema volume with a mean 3.363±0.023 at 4 h. Conclusions: This study confirmed the analgesic and anti-inflammatory properties of Narcine brunnea observed during the ethno-pharmacological survey. In order to go towards a valuation of this traditional knowledge, further studies like purification, isolation and NMR must be carried out to determine which of these compounds are actually responsible for such properties.

  3. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Science.gov (United States)

    Laloy, J.; Lozano, O.; Alpan, L.; Masereel, B.; Toussaint, O.; Dogné, J. M.; Lucas, S.

    2015-08-01

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  4. Titanium oxide (TiO2) nanoparticles in induction of apoptosis and inflammatory response in brain

    Science.gov (United States)

    Meena, Ramovatar; Kumar, Sumit; Paulraj, R.

    2015-01-01

    The ever increasing applications of engineered nanoparticles in 21st century cause serious concern about its potential health risks on living being. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines. In order to study the mechanism underlying the effects of nano-TiO2 (TiO2 nanoparticles) on the brain, wistar rats were administrated intravenously with various doses of nano-TiO2 (21 nm) through the caudal vein, once a week for 4 weeks and different parameters such as bioaccumulation of nano-TiO2, oxidative stress-mediated response, level of inflammatory markers such as NF-κB (p65), HSP 60, p38, nitric oxide, IFN-γ and TNF-α, and level of neurochemicals in brain as well as DNA damage and expression of apoptosis markers (p53, Bax, Bcl-2, and cyto c) were evaluated. Results show that the concentration of nano-TiO2 in the brain increased with increasing the doses of nano-TiO2. Oxidative stress and injury of the brain occurred as nano-TiO2 appeared to trigger a cascade of reactions such as inflammation, lipid peroxidation, decreases the activities of antioxidative enzymes and melatonin level, the reduction of glutamic acid, downregulated levels of acetylcholinesterase activities, and the increase in caspase-3 activity (a biomarker of apoptosis), DNA fragmentation, and apoptosis. It may be concluded that nano-TiO2 induces oxidative stress that leads to activation of inflammatory cytokines and an alteration in the level of neurotransmitters resulted in the induction of mitochondrial-mediated apoptosis.

  5. Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

    Science.gov (United States)

    Narita, N; Kumar, N; Cherkas, P S; Chiang, C Y; Dostrovsky, J O; Coderre, T J; Sessle, B J

    2012-08-30

    Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), ppain model, and that it may prove useful for the treatment of orofacial inflammatory pain states. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Annexin A1 Is Involved in the Resolution of Inflammatory Responses during Leishmania braziliensis Infection.

    Science.gov (United States)

    Oliveira, Leandro G; Souza-Testasicca, Míriam C; Vago, Juliana P; Figueiredo, Amanda Braga; Canavaci, Adriana M C; Perucci, Luiza Oliveira; Ferreira, Tatiana P Teixeira; Coelho, Eduardo A F; Gonçalves, Denise Utsch; Rocha, Manoel Otávio C; E Silva, Patrícia M R; Ferreira, Cláudia N; Queiroz-Junior, Celso; Sousa, Lirlândia P; Fernandes, Ana Paula

    2017-03-13

    Leishmaniases are diseases caused by several Leishmania species. Leishmania (Viannia) braziliensis can cause localized cutaneous leishmaniasis (LCL), which heals spontaneously, or mucosal leishmaniasis (ML), characterized by chronic and intense inflammation and scanty parasitism. Annexin A1 (AnxA1) is a protein involved in modulation and resolution of inflammation through multiple mechanisms. In the present study, the role of AnxA1 was investigated in L. braziliensis-infected BALB/c mice. AnxA1 levels increased at the peak of tissue lesion and parasitism in infected mice. AnxA1 increased also after L. braziliensis infection of BALB/c (wild-type [WT]) bone marrow derived macrophages. Despite a lower parasite intake, parasite burden in bone marrow-derived macrophages from AnxA1(-/-) mice was similar to WT and associated with an early increase of TNF-α and, later, of IL-10. AnxA1(-/-) mice controlled tissue parasitism similarly to WT animals, but they developed significantly larger lesions at later stages of infection, with a more pronounced inflammatory infiltrate and increased specific production of IFN-γ, IL-4, and IL-10. AnxA1(-/-) mice also presented higher phosphorylation levels of ERK-1/2 and p65/RelA (NF-κB) and inducible NO synthase expression, suggesting that AnxA1 may be involved in modulation of inflammation in this model of experimental leishmaniasis. Finally, assessment of AnxA1 levels in sera from patients with LCL or ML revealed that ML patients had higher levels of serum AnxA1 than did LCL patients or control subjects. Collectively, these data indicate that AnxA1 is actively expressed during L. braziliensis infection. In the absence of AnxA1, mice are fully able to control parasite replication, but they present more intense inflammatory responses and delayed ability to resolve their lesion size.

  7. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Energy Technology Data Exchange (ETDEWEB)

    Laloy, J., E-mail: julie.laloy@unamur.be [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lozano, O. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Alpan, L.; Masereel, B. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Toussaint, O. [University of Namur (UNamur), Laboratory of Cellular Biochemistry and Biology (URBC), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Dogné, J. M. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lucas, S. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium)

    2015-08-15

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  8. The localisation of inflammatory cells and expression of associated proteoglycans in response to implanted chitosan.

    Science.gov (United States)

    Farrugia, Brooke L; Whitelock, John M; Jung, MoonSun; McGrath, Barbara; O'Grady, Robert L; McCarthy, Simon J; Lord, Megan S

    2014-02-01

    Implantation of a foreign material almost certainly results in the formation of a fibrous capsule around the implant however, mechanistic events leading to its formation are largely unexplored. Mast cells are an inflammatory cell type known to play a role in the response to material implants, through the release of pro-inflammatory proteases and cytokines from their α-granules following activation. This study examined the in vivo and in vitro response of mast cells to chitosan, through detection of markers known to be produced by mast cells or involved with the inflammatory response. Mast cells, identified as Leder stained positive cells, were shown to be present in response to material implants. Additionally, the mast cell receptor, c-kit, along with collagen, serglycin, perlecan and chondroitin sulphate were detected within the fibrous capsules, where distribution varied between material implants. In conjunction, rat mast cells (RBL-2H3) were shown to be activated following exposure to chitosan as indicated by the release of β-hexosaminidase. Proteoglycan and glycosaminoglycans produced by the cells showed similar expression and localisation when in contact with chitosan to when chemically activated. These data support the role that mast cells play in the inflammatory host response to chitosan implants, where mediators released from their α-granules impact on the formation of a fibrous capsule by supporting the production and organisation of collagen fibres.

  9. Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Bor-Ren [Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, Taiwan (China); Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China); Tsai, Cheng-Fang [Department of Biotechnology, Asia University, Taichung, Taiwan (China); Lin, Hsiao-Yun [Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Tseng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua County, Taiwan (China); Huang, Shiang-Suo [Department of Pharmacology and Institute of Medicine, College of Medicine, Chung Shan Medical University, Taiwan (China); Wu, Chi-Rei [Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taiwan (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan (China); Yeh, Wei-Lan [Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan (China); Lu, Dah-Yuu, E-mail: dahyuu@mail.cmu.edu.tw [Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan (China)

    2013-05-15

    We investigated the interaction between proinflammatory and inflammatory responses caused by Staphylococcus aureus-derived lipoteichoic acid (LTA) in primary cultured microglial cells and BV-2 microglia. LTA induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels increase in a concentration- and time-dependent manner. Meanwhile, LTA also increased nitric oxide (NO) and PGE{sub 2} production in microglia. Administration of TLR2 antagonist effectively inhibited LTA-induced NO, iNOS, and COX-2 expression. Moreover, treatment of cells with LTA caused a time-dependent activation of ERK, p38, JNK, as well as AKT. We also found that LTA-induced iNOS and COX-2 up-regulation were attenuated by p38, JNK, and PI3-kinase inhibitors. On the other hand, LTA-enhanced HO-1 expression was attenuated by p38 and PI3-kinase inhibitors. Treatment of cells with NF-κB and AP-1 inhibitors antagonized LTA-induced iNOS and COX-2 expression. However, only NF-κB inhibitors reduced LTA-induced HO-1 expression in microglia. Furthermore, stimulation of cells with LTA also activated IκBα phosphorylation, p65 phosphorylation at Ser{sup 536}, and c-Jun phosphorylation. Moreover, LTA-induced increases of κB-DNA and AP-1-DNA binding activity were inhibited by p38, JNK, and PI3-kinase inhibitors. HO-1 activator CoPP IX dramatically reversed LTA-induced iNOS expression. Our results provided mechanisms linking LTA and inflammation/anti-inflammation, and indicated that LTA plays a regulatory role in microglia activation. - Highlights: • LTA causes an increase in iNOS, COX-2, and HO-1 expression in microglia. • LTA induces iNOS and COX-2 expression through TLR-2/NF-κB and AP-1 pathways. • HO-1 expression is regulated through p38, JNK, PI3K/AKT and AP-1 pathways. • Induced HO-1 reduces LTA-induced iNOS expression. • LTA plays a regulatory role on inflammatory/anti-inflammatory responses.

  10. An Algorithm for Systemic Inflammatory Response Syndrome Criteria-Based Prediction of Sepsis in a Polytrauma Cohort.

    Science.gov (United States)

    Lindner, Holger A; Balaban, Ümniye; Sturm, Timo; Weiß, Christel; Thiel, Manfred; Schneider-Lindner, Verena

    2016-12-01

    Lifesaving early distinction of infectious systemic inflammatory response syndrome, known as "sepsis," from noninfectious systemic inflammatory response syndrome is challenging in the ICU because of high systemic inflammatory response syndrome prevalence and lack of specific biomarkers. The purpose of this study was to use an automatic algorithm to detect systemic inflammatory response syndrome criteria (tachycardia, tachypnea, leukocytosis, and fever) in surgical ICU patients for ICU-wide systemic inflammatory response syndrome prevalence determination and evaluation of algorithm-derived systemic inflammatory response syndrome descriptors for sepsis prediction and diagnosis in a polytrauma cohort. Cross-sectional descriptive study and retrospective cohort study. Electronic medical records of a tertiary care center's surgical ICU, 2006-2011. All ICU admissions and consecutive polytrauma admissions. None. Average prevalence of conventional systemic inflammatory response syndrome (≥ 2 criteria met concomitantly) from cross-sectional application of the algorithm to all ICU patients and each minute of the study period was 43.3%. Of 256 validated polytrauma patients, 85 developed sepsis (33.2%). Three systemic inflammatory response syndrome descriptors summarized the 24 hours after admission and before therapy initiation: 1) systemic inflammatory response syndrome criteria average for systemic inflammatory response syndrome quantification over time, 2) first-to-last minute difference for trend detection, and 3) change count reflecting systemic inflammatory response syndrome criteria fluctuation. Conventional systemic inflammatory response syndrome for greater than or equal to 1 minute had 91% sensitivity and 19% specificity, whereas a systemic inflammatory response syndrome criteria average cutoff value of 1.72 had 51% sensitivity and 77% specificity for sepsis prediction. For sepsis diagnosis, systemic inflammatory response syndrome criteria average and first

  11. Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

    DEFF Research Database (Denmark)

    Villadsen, Louise S; Skov, Lone; Baadsgaard, Ole

    2003-01-01

    and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies......In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness......, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress....

  12. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

  13. Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria.

    Science.gov (United States)

    Yu, Yanbao; Zielinski, Martin D; Rolfe, Melanie A; Kuntz, Melissa M; Nelson, Heidi; Nelson, Karen E; Pieper, Rembert

    2015-10-01

    Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB4 and LTC4, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Institute of Scientific and Technical Information of China (English)

    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective:To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).Data Sources:We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators).The following terms were used:"inflammatory bowel disease (IBD)" OR "Cmhn's disease" OR "ulcerative colitis"AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators."Study Selection:The inclusion criteria of articles were that the studies:(1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical,radiographic,endoscopic,and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping,15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy,antibiotics only,mesalazine only,biological agent only such as infliximab,adalimumab,certolizumab or natalizumab or within 3 months of stopping one of these agents).The exclusion criteria of articles were that the studies:(1) History of hepatitis B virus (HBV),influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV,influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g.chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.Results:Patients treated with immunomodulators were associated with lower response rates to vaccination

  15. Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations.

    Science.gov (United States)

    Papaioannou, Vasilios; Pneumatikos, Ioannis; Maglaveras, Nikos

    2013-01-01

    Many experimental and clinical studies have confirmed a continuous cross-talk between both sympathetic and parasympathetic branches of autonomic nervous system and inflammatory response, in different clinical scenarios. In cardiovascular diseases, inflammation has been proven to play a pivotal role in disease progression, pathogenesis and resolution. A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals' processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers. However, a lot of open questions remain to be addressed, regarding the existence of a true association between heart rate variability and autonomic nervous system output or its adoption for risk stratification and therapeutic monitoring at the bedside. Finally, potential therapeutic implications will be discussed, leading to autonomic balance restoration in relation with inflammatory control.

  16. The effect of dietary fatty acids on post-operative inflammatory response in a porcine model

    DEFF Research Database (Denmark)

    Langerhuus, Sine Nygaard; Jensen, Karin Hjelholt; Tønnesen, Else Kirstine

    2012-01-01

    The potential anti-inflammatory effects of dietary fish oil (FO) have been studied in numerous clinical trials. However, variation in lifestyle and morbidity among patients can be difficult to control. In the present study, the impact of a 3-week dietary pre-treatment with 10% (w/w) FO (n 28......), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 ...-operative response in a number of inflammatory markers was affected by FO, and this was most apparent compared with SO....

  17. Ultraporous interweaving electrospun microfibers from PCL-PEO binary blends and their inflammatory responses

    Science.gov (United States)

    Li, Yan-Fang; Rubert, Marina; Aslan, Hüsnü; Yu, Ying; Howard, Kenneth A.; Dong, Mingdong; Besenbacher, Flemming; Chen, Menglin

    2014-02-01

    Production of one dimensional nanomaterials with secondary morphology exhibiting unique functions is challenging. Here we report for the first time that a nanoscale immiscible polymer blend solution electrojet can assemble into ultraporous interweaving microfibers. This intriguingly novel morphology originated from a blend of polycaprolactone (PCL) and polyethylene oxide (PEO) in a DCM-DMF mixed solution when the ratio between each component reached a threshold and when the electrospinning parameters were delicately controlled. The morphology, crystallinity, surface chemistry and wettabilities were characterized to understand the mechanism of formation. The interplay of the two semi-crystalline polymers and the pair of solvents/non-solvents with the electrospinning processing parameters was found to be critical for the formation of the unique structure. Furthermore, the interesting combination of biocompatible, biodegradable PCL with protein-resistant PEO motivated us to assess its inflammation responses on the RAW 264.7 macrophage cell line. All fibers were found to be biocompatible with low inflammation potential upon incubation, while compared with pure PCL nanofibers; the unique interweaving microfibers induced a slightly higher inflammatory reaction.Production of one dimensional nanomaterials with secondary morphology exhibiting unique functions is challenging. Here we report for the first time that a nanoscale immiscible polymer blend solution electrojet can assemble into ultraporous interweaving microfibers. This intriguingly novel morphology originated from a blend of polycaprolactone (PCL) and polyethylene oxide (PEO) in a DCM-DMF mixed solution when the ratio between each component reached a threshold and when the electrospinning parameters were delicately controlled. The morphology, crystallinity, surface chemistry and wettabilities were characterized to understand the mechanism of formation. The interplay of the two semi-crystalline polymers and the

  18. A novel marker for the assessment of the treatment result in pelvic inflammatory disease.

    Science.gov (United States)

    Akopuz, Aycan; Turan, Volkan; Ozcan, Aycut; Kopuz, Yeliz; Toz, Emrah; Kurt, Sefa

    2016-04-01

    Although various laboratory tests have been studied with an intended use in the diagnosis of pelvic inflammatory disease (PID) and the assessment of treatment response, the neutrophil/lymphocyte ratio (NLR) has not been investigated in PID. We aimed to explore the value of blood NLR in diagnosis of PID and assessment of the treatment response. Sixty-five patients followed-up and treated with the diagnosis of PID in Izmir Tepecik Training and Research Hospital were retrospectively reviewed. The NLR measured before treatment and after clinical remission in the patients diagnosed with PID were assessed and compared with controls (N.=65). In the patient group, the NLR measured before treatment was statistically significantly higher than the NLR measured after clinical remission (6.9±6.4 vs. 2.03±0.8, P<0.001). Similarly, comparison of the NLR measured in the patient group before treatment with the control group showed that this ratio was statistically significantly higher in the patient group before treatment (6.9±6.4 vs. 1.9±0.5, P<0.001). A comparison of the NLR measured after clinical remission did not reveal a statistically significant difference when compared with control group (1.9±0.5 vs. 2.03±0.8, P=0.981). The NLR increases in patients diagnosed with PID and returns to normal levels when the patients enter clinical remission. Since there is currently no laboratory test available that indicates clinical improvement by returning to normal levels, as achieved by the NLR, and since it is an inexpensive and easy-to-apply test, we suggest that the NLR can be conveniently used to show clinical improvement in PID.

  19. Histamine regulates the inflammatory response of the tunicate Styela plicata.

    Science.gov (United States)

    García-García, Erick; Gómez-González, Nuria E; Meseguer, José; García-Ayala, Alfonsa; Mulero, Victoriano

    2014-10-01

    Histamine is stored inside hemocytes of the tunicate Styela plicata (Chordata, Tunicata, Ascidiacea), but no evidence on its role in the regulation of the immune response of this species has been reported. We examined whether histamine participated in the regulation of inflammation and host defense in S. plicata. The presence of histamine inside S. plicata hemocytes was confirmed by flow cytometry, and histamine release was detected by ELISA, after in vitro hemocyte stimulation with different PAMPs. In vitro hemocyte treatment with histamine, or specific histamine-receptor agonists, reduced their phagocytic ability. Injection of histamine into the tunic recruited hemocytes to the site of injection. Systemic injection of histamine, or the histamine-releasing agent compound 48/80, decreased the phagocytic ability of hemocytes. Histamine promoted the constriction of tunic hemolymph vessels in vivo, having a direct effect on vasoconstriction in tunic explants. These results provide for the first time clear evidence for the involvement of histamine in the regulation of inflammation and host defense in tunicates.

  20. Antibody Response against Parvovirus in Patients with Inflammatory Rheumatological Diseases

    Directory of Open Access Journals (Sweden)

    SH Raeisi

    2011-07-01

    Full Text Available Introduction: Some viral infections have been suggested to trigger or cause autoimmune diseases. One of these viruses is parvovirus B19 which can have various rheumatologic manifestations. In this study we investigated the association between parvovirus and rheumatoid arthritis (RA, systemic lupus erythematosis(SLE, systemic sclerosis(SSc and undifferentiated arthritis at the Rheumatological Clinic, Imam Khomeini hospital. Methods: In this sectional case-control study, IgM and IgG antibodies against parvovirus B19 were measured with ELISA in 41 patients with RA, 28 patients with SLE, 13 patients with SSc, 8 patients with undifferentiated arthritis as well as 90 healthy controls. The ELISA kit (DRG, Germany was semi-quantitative and qualititative. Results: Parvovirus B19 IgM was detected in one patient with RA, one with SSc and four in the control group. IgG anti- B19-specific antibody was detected in 58.5% of RA patients, 67.9% of SLE patients, 69. 2% of SSc patients, 87.5% of undifferentiated arthritis patients as compared to 53.3% of controls. The results were compared between the patient and control groups(p>0.05. Conclusion: According to the results, there was no significant correlation for the antibody titer against parvovirus B19 in the patient and control group. The highly positive response of IgG against parvovirus in undifferentiated arthritis implies the need for more research.

  1. Trichothecene mycotoxins activate inflammatory response in human macrophages.

    Science.gov (United States)

    Kankkunen, Päivi; Rintahaka, Johanna; Aalto, Annika; Leino, Marina; Majuri, Marja-Leena; Alenius, Harri; Wolff, Henrik; Matikainen, Sampsa

    2009-05-15

    Damp building-related illnesses have caused concern for years in many countries. Although the problem is extensive, the knowledge of the immunological reactions behind damp building-related illnesses is still quite limited. Trichothecene mycotoxins form one major group of toxins, which possibly contribute to the illnesses. Stachybotrys chartarum is a well-known, but also controversial damp building mold and many strains of this mold are capable of producing trichothecenes. In this report, we have examined the effect of S. chartarum and trichothecene mycotoxins on the proinflammatory cytokine response in human macrophages. As a result, satratoxin-positive S. chartarum activated inflammasome-associated caspase-1, which is needed for proteolytic processing of IL-1beta and IL-18. Furthermore, purified trichothecene mycotoxins, roridin A, verrucarin A, and T-2 toxin activated caspase-1, and these mycotoxins also strongly enhanced LPS-dependent secretion of IL-1beta and IL-18. The satratoxin-positive strain of S. chartarum and the trichothecenes also triggered the activation of caspase-3, which is an effector caspase of apoptosis. Satratoxin-negative S. chartarum was not able to activate either caspase-1 or caspase-3. In conclusion, our results indicate that human macrophages sense trichothecene mycotoxins as a danger signal, which activates caspase-1, and further enables the secretion of IL-1beta and IL-18 from the LPS-primed cells.

  2. Cohabitation with a sick partner increases allergic lung inflammatory response in mice.

    Science.gov (United States)

    Hamasato, Eduardo Kenji; de Lima, Ana Paula Nascimento; de Oliveira, Ana Paula Ligeiro; dos Santos Franco, Adriana Lino; de Lima, Wothan Tavares; Palermo-Neto, João

    2014-11-01

    The bidirectional relationship between the nervous system and the immune system is relevant for homeostatic organism maintenance. Studies from our laboratory showed that 14days of cohabitation with a sick partner (injected with Ehrlich tumor cells-TAE) produced behavioral, neurochemical, endocrinological and immunological changes. This study analyzes the effects of cohabitation with an Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory response in mice. Pairs of male mice were divided into three groups: naïve, control and experimental. Animals of the naïve group were kept undisturbed being used for the assessment of basal parameters. One animal of each experimental and control pair of mice was immunized with OVA. On ED(0), these OVA-immunized animals received an OVA booster. At this day (D(0)) the experimental mice that were kept undisturbed were inoculated with 5×10(6) Ehrlich tumor cells; their immunized cage-mates were then referred as to CSP ("companion of sick partner"). The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9% NaCl; their sensitized cage-mates were subsequently referred as CHP ("companion of health partner"). The OVA challenge was performed on CSP and CHP mice on ED(12) and ED(13); blood and tissue collection were performed on ED(14). Fourteen days after cohabitation, in comparison to the CHP mice, the CSP mice displayed the following: (1) an increased number of eosinophils and neutrophils in the BAL, (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and decreased levels of IL-10 and IFN-γ in the BAL supernatant, (5) increased levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific IgE in the peripheral blood, (6) increased expression of L-selectin in the BAL granulocytes, (7) decreased tracheal reactivity to methacholine measured in vitro, (8) no changes in plasma corticosterone levels and (9) increased levels of plasmatic noradrenaline. These

  3. Expression of Drosophila adenosine deaminase in immune cells during inflammatory response.

    Science.gov (United States)

    Novakova, Milena; Dolezal, Tomas

    2011-03-11

    Extra-cellular adenosine is an important regulator of inflammatory responses. It is generated from released ATP by a cascade of ectoenzymes and degraded by adenosine deaminase (ADA). There are two types of enzymes with ADA activity: ADA1 and ADGF/ADA2. ADA2 activity originates from macrophages and dendritic cells and is associated with inflammatory responses in humans and rats. Drosophila possesses a family of six ADGF proteins with ADGF-A being the main regulator of extra-cellular adenosine during larval stages. Herein we present the generation of a GFP reporter for ADGF-A expression by a precise replacement of the ADGF-A coding sequence with GFP using homologous recombination. We show that the reporter is specifically expressed in aggregating hemocytes (Drosophila immune cells) forming melanotic capsules; a characteristic of inflammatory response. Our vital reporter thus confirms ADA expression in sites of inflammation in vivo and demonstrates that the requirement for ADA activity during inflammatory response is evolutionary conserved from insects to vertebrates. Our results also suggest that ADA activity is achieved specifically within sites of inflammation by an uncharacterized post-transcriptional regulation based mechanism. Utilizing various mutants that induce melanotic capsule formation and also a real immune challenge provided by parasitic wasps, we show that the acute expression of the ADGF-A protein is not driven by one specific signaling cascade but is rather associated with the behavior of immune cells during the general inflammatory response. Connecting the exclusive expression of ADGF-A within sites of inflammation, as presented here, with the release of energy stores when the ADGF-A activity is absent, suggests that extra-cellular adenosine may function as a signal for energy allocation during immune response and that ADGF-A/ADA2 expression in such sites of inflammation may regulate this role.

  4. Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

    Directory of Open Access Journals (Sweden)

    Jueun Oh

    2012-01-01

    Full Text Available Carnosic acid (CA is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS and retinoic acid (RA. In addition, CA blocked the release of nitric oxide (NO, tumor necrosis factor (TNF-α, and prostaglandin E2 (PGE2 from RAW264.7 cells activated by the toll-like receptor (TLR-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS. CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K, Akt, inhibitor of κBα (IκBα kinase (IKK, and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.

  5. YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia

    Directory of Open Access Journals (Sweden)

    Bubeck Sarah S

    2010-06-01

    Full Text Available Abstract Background Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues. Results Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection. Conclusions Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.

  6. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology.

    Science.gov (United States)

    Millar, Jonathan E; Fanning, Jonathon P; McDonald, Charles I; McAuley, Daniel F; Fraser, John F

    2016-11-28

    Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient's blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

  7. Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Owens, Trevor

    2010-01-01

    Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I I...

  8. Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling

    Directory of Open Access Journals (Sweden)

    Dan Yang

    2016-02-01

    Full Text Available Background/Aims: Comparative gene identification-58 (CGI-58, an adipose triglyceride lipase (ATGL coactivator, strongly promotes ATGL-mediated triglyceride (TG catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG and wild type mice (WT were fed a high fat diet (HFD, and RAW264.7 cells were treated with lipopolysaccharide (LPS. The peroxisome proliferator-activated receptor (PPAR signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.

  9. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome

    NARCIS (Netherlands)

    S.S. Iyer; W.P. Pulskens; J.J. Sadler; L.M. Butter; G.J. Teske; T.K. Ulland; S.C. Eisenbarth; S. Florquin; R.A. Flavell; J.C. Leemans; F.S. Sutterwala

    2009-01-01

    Dying cells are capable of activating the innate immune system and inducing a sterile inflammatory response. Here, we show that necrotic cells are sensed by the Nlrp3 inflammasome resulting in the subsequent release of the proinflammatory cytokine IL-1 beta. Necrotic cells produced by pressure disru

  10. Considering depression as a consequence of activation of the inflammatory response system

    NARCIS (Netherlands)

    Korf, J; Klein, HC; Versijpt, J; den Boer, J; ter Horst, GJ

    This paper summarizes the possible interrelation between peripheral and/or cerebral inflammation and depression. Often, depression is regarded as a consequence of life events, including disabling diseases. The question addressed here is whether activation of the inflammatory response system (IRS)

  11. Dietary L-arginine supplementation modulates lipopolysaccharide-induced systemic inflammatory response in broiler chickens

    Science.gov (United States)

    This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate lipopolysaccharide (LPS)-induced systemic inflammatory response through LPS/TLR-4 signaling pathway in broilers. The experiment was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatm...

  12. Influence of the blood bacterial load on the meningeal inflammatory response in Streptococcus pneumoniae meningitis

    DEFF Research Database (Denmark)

    Østergaard, C; O´Reilly, T; Brandt, C;

    2006-01-01

    BACKGROUND: Despite bacteraemia is present in the majority of patients with pneumococcal, little is known about the influence of the systemic infection on the meningeal inflammatory response. METHODS: To explore the role of systemic infection on the meningeal inflammation, experimental meningitis...

  13. Dietary L-arginine supplementation attenuates lipopolysaccharide-induced inflammatory response in broiler chickens

    Science.gov (United States)

    Two experiments were conducted to investigate the effect of dietary L-arginine (Arg) supplementation on inflammatory response and innate immunity of broilers. Experiment 1 was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatment; 6 birds/cage) with 3 dietary Arg concentrations (1.05, 1.4...

  14. Regulation of Inflammatory Responses in Shock-Related Syndromes by Synthetic Oligopeptides and Steroids

    NARCIS (Netherlands)

    M. van der Zee (Marten)

    2010-01-01

    textabstractInflammation is the body’s way of responding to disturbances in homeostasis. Depending on the triggering event and the site of inflammation, the inflammatory response has different physiological purposes and pathological consequences (Figure 1). Inducers of inflammation are either foreig

  15. The levels of RAC3 expression are up regulated by TNF in the inflammatory response.

    Science.gov (United States)

    Alvarado, Cecilia Viviana; Rubio, María Fernanda; Fernández Larrosa, Pablo Nicolas; Panelo, Laura Carolina; Azurmendi, Pablo Javier; Ruiz Grecco, Marina; Martínez-Nöel, Giselle Astrid; Costas, Mónica Alejandra

    2014-01-01

    RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB) that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF), one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Our results suggest that increase of RAC3 during the inflammatory response could be a molecular mechanism involved in the control of sensitivity to both pro- and anti-inflammatory stimuli in order to maintain the normal healthy course of the immune response.

  16. The time course of the inflammatory response to the Salmonella typhi vaccination

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Bosch, J.A.; Drayson, M.T.; Veldhuijzen van Zanten, J.J.C.S.

    2013-01-01

    The Salmonella typhi vaccination induces transient increases in inflammatory-responsive cytokines and molecules. For instance, it causes small, mild increases in interleukin-6 (IL-6) within a few hours and C-reactive protein (CRP) within 24 h. No study has charted either the time course of the infla

  17. A biomarker panel to discriminate between systemic inflammatory response syndrome SIRS and sepsis and sepsis severity

    NARCIS (Netherlands)

    Punyadeera, C.; Schneider, E. M.; Schaffer, D.; Hsu, H-Y.; Joos, T.O.; Kriebel, F; Weiss, M.; Verhaegh, W.F.J.

    2009-01-01

    In this study we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) vs. sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients wh

  18. A biomarker panel to discriminate between systemic inflammatory response syndrome SIRS and sepsis and sepsis severity

    NARCIS (Netherlands)

    Punyadeera, C.; Schneider, E. M.; Schaffer, D.; Hsu, H-Y.; Joos, T.O.; Kriebel, F; Weiss, M.; Verhaegh, W.F.J.

    2009-01-01

    In this study we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) vs. sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients

  19. Progressive loss of nigrostriatal dopaminergic neurons induced by inflammatory responses to fipronil.

    Science.gov (United States)

    Park, Jae Hyeon; Park, Youn Sun; Koh, Hyun Chul

    2016-09-06

    Inflammatory responses are involved in mechanisms of neuronal cell damage in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). We investigated the mechanisms whereby inflammatory responses contribute to loss of dopaminergic neurons in fipronil (FPN)-treated rats. After stereotaxic injection of FPN in the substantia nigra (SN), the number of tyrosine hydroxylase (TH)-positive neurons and the levels of TH expression in the SN decreased at 7days, and a significant decrease was observed at 14days with a subsequent reduction in striatal TH expression. Decreases in dopamine (DA) levels, however, began at 3days post-injection, preceding the changes in TH expression. In contrast, glial fibrillary acidic protein (GFAP) expression was significantly increased at 3days and persisted for up to 14days post-lesion; these changes in GFAP expression appeared to be inversely correlated with TH expression. Furthermore, we found that FPN administration induced an inflammatory response characterized by increased levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α), which was mediated by activated microglia following infusion of FPN unilaterally into the SN. Intranigral injection of FPN underwent an inflammatory response with a resultant ongoing loss of dopaminergic neurons, indicating that pesticides may have important implication for the study of PD. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Considering depression as a consequence of activation of the inflammatory response system

    NARCIS (Netherlands)

    Korf, J; Klein, HC; Versijpt, J; den Boer, J; ter Horst, GJ

    2002-01-01

    This paper summarizes the possible interrelation between peripheral and/or cerebral inflammation and depression. Often, depression is regarded as a consequence of life events, including disabling diseases. The question addressed here is whether activation of the inflammatory response system (IRS) ca

  1. Corticosterone treatment of pregnant low dose endotoxin-treated rats : Inhibition of the inflammatory response

    NARCIS (Netherlands)

    Faas, MM; Slot, K; Koiter, TR; Schuiling, GA

    2000-01-01

    PROBLEM: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone? METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% choleste

  2. The levels of RAC3 expression are up regulated by TNF in the inflammatory response

    Directory of Open Access Journals (Sweden)

    Cecilia Viviana Alvarado

    2014-01-01

    Full Text Available RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF, one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Our results suggest that increase of RAC3 during the inflammatory response could be a molecular mechanism involved in the control of sensitivity to both pro- and anti-inflammatory stimuli in order to maintain the normal healthy course of the immune response.

  3. The systemic inflammatory response syndrome predicts short-term outcome after transapical transcatheter aortic valve implantation

    NARCIS (Netherlands)

    Rettig, Thijs C D; Rigter, Sander; Nijenhuis, Vincent J.; Van Kuijk, Jan Peter; Ten Berg, Jurriën M.; Heijmen, Robin H.; Van De Garde, Ewoudt M W; Noordzij, Peter G.

    2015-01-01

    Objective Despite the minimally invasive nature of transcatheter aortic valve implantation (TAVI), the incidence of acute kidney injury (AKI) and mortality is of major concern. Several studies showed that outcome was influenced by the systemic inflammatory response syndrome (SIRS) in patients underg

  4. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting

    NARCIS (Netherlands)

    Gu, YJ; Mariani, MA; van Oeveren, W; Grandjean, JG; Boonstra, PW

    1998-01-01

    Background. The aim of this prospective study was to determine whether the inflammation-associated clinical morbidity as well as the subclinical markers of the inflammatory response are reduced in patients who undergo minimally invasive coronary artery bypass grafting without cardiopulmonary bypass.

  5. Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

    Directory of Open Access Journals (Sweden)

    Hey-Kyeong Jeong

    Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

  6. Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Natalia Niedziela

    2016-01-01

    Full Text Available The role of nitric oxide and its reactive derivatives (NOx is well known in the pathogenesis of multiple sclerosis, which is an inflammatory disease while NOx seems to be important in coordinating inflammatory response. The purpose of the present study was to assess serum NOx as one of the nitrogen species and inflammatory parameters in relapsing-remitting multiple sclerosis patients and to compare the effectiveness of various types of disease-modifying therapies that reduce nitric oxide and inflammatory biomarkers. Elevated NOx level was observed in patients who received the first-line disease-modifying therapy (interferons beta-1a and beta-1b in comparison with the subjects treated with the second-line disease-modifying therapy (natalizumab; fingolimod and healthy controls without significant differences in C-reactive protein and interleukin-1 beta. A negative correlation was observed between serum NOx level and the duration of multiple sclerosis confirmed in the whole study population and in subjects treated with the first-line agents. Only serum NOx, concentration could reveal a potential efficacy of disease-modifying therapy with a better reduction in NOx level due to the second-line agents of disease-modifying therapy.

  7. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Jill K Terra

    2011-12-01

    Full Text Available Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT, as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6 background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  8. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

    Science.gov (United States)

    Terra, Jill K; France, Bryan; Cote, Christopher K; Jenkins, Amy; Bozue, Joel A; Welkos, Susan L; Bhargava, Ragini; Ho, Chi-Lee; Mehrabian, Margarete; Pan, Calvin; Lusis, Aldons J; Davis, Richard C; LeVine, Steven M; Bradley, Kenneth A

    2011-12-01

    Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  9. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

    Directory of Open Access Journals (Sweden)

    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  10. Modulatory Effect of Gliadin Peptide 10-mer on Epithelial Intestinal CACO-2 Cell Inflammatory Response.

    Directory of Open Access Journals (Sweden)

    Antonella Capozzi

    Full Text Available Celiac Disease (CD is a chronic inflammatory enteropathy, triggered in genetically susceptible individuals by dietary gluten. Gluten is able to elicit proliferation of specific T cells and secretion of inflammatory cytokines in the small intestine. In this study we investigated the possibility that p10-mer, a decapeptide from durum wheat (QQPQDAVQPF, which was previously shown to prevent the activation of celiac peripheral lymphocytes, may exert an inhibitory effect on peptic-tryptic digested gliadin (PT-Gly-stimulated intestinal carcinoma CACO-2 cells. In these cells, incubated with PT-Gly or p31-43 α-gliadin derived peptide in the presence or in the absence of p10-mer, IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation were measured by immunoblotting, Cyclooxigenase 2 (COX-2 activity by PGE-2 release assay, and production of cytokines in the cell supernatants by ELISA. Our results showed that pre-treatment of CACO-2 cells with p10-mer significantly inhibited IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation, as well as COX-2 activity (i.e. PGE-2 release and production of the IL-6 and IL-8 pro-inflammatory cytokines, induced by gliadin peptides. These findings demonstrate the inhibitory effect of the p10-mer peptide on inflammatory response in CACO-2 cells. The results of the present study show that this p10-mer peptide can modulate "in vitro" the inflammatory response induced by gliadin peptides, allowing to move towards new therapeutic strategies. Turning off the inflammatory response, may in fact represent a key target in the immunotherapy of celiac disease.

  11. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk

    Science.gov (United States)

    Lin, Zongwei; Ge, Junfeng; Wang, Zhe; Ren, Jianwei; Wang, Xiaowei; Xiong, Hui; Gao, Jing; Zhang, Yan; Zhang, Qunye

    2017-01-01

    The inflammatory responses of vascular endothelial cells (VECs) are critical in the development of many cardio-cerebrovascular diseases. Let-7e is an important regulator of endothelial function and inflammation. However, the effects and mechanisms of let-7e on VECs inflammation have not been studied until recently. Thus, we investigated these issues and found that in addition to proliferation, apoptosis and cell adhesion, let-7e was also implicated in the regulation of inflammatory responses through a complex network, including IκBβ and lncRNA lnc-MKI67IP-3. Let-7e promoted NF-κB activation and translocation to the nucleus by inhibiting its target gene (IκBβ) expression and subsequently increased the expression of inflammatory and adhesion molecules. Meanwhile, lnc-MKI67IP-3 acted as a sponge or competing endogenous RNA (ceRNA) for let-7e, suppressing its pro-inflammatory effects, and let-7e decreased lnc-MKI67IP-3 expression, thereby forming a positive feedback loop to aggravate inflammation. Moreover, let-7e, lnc-MKI67IP-3 and IκBβ were also abnormal in oxLDL-treated VECs and atherosclerotic plaques. The present study revealed let-7e as a pro-inflammatory mediator and a novel regulatory mechanism for the NF-κB pathway through ceRNA crosstalk, comprising let-7e and its target IκBβ and the ceRNA lnc-MKI67IP-3. Thus, this molecule might play important roles in the inflammatory responses of VECs and development of atherosclerosis. PMID:28195197

  12. Power Doppler ultrasonographic assessment of the ankle in patients with inflammatory rheumatic diseases.

    Science.gov (United States)

    Suzuki, Takeshi

    2014-11-18

    Ankle involvement is frequent in patients with inflammatory rheumatic diseases, but accurate evaluation by physical examination is often difficult because of the complex anatomical structures of the ankle. Over the last decade, ultrasound (US) has become a practical imaging tool for the assessment of articular and periarticular pathologies, including joint synovitis, tenosynovitis, and enthesitis in rheumatic diseases. Progress in power Doppler (PD) technology has enabled evaluation of the strength of ongoing inflammation. PDUS is very useful for identifying the location and kind of pathologies in rheumatic ankles as well as for distinguishing between inflammatory processes and degenerative changes or between active inflammation and residual damage. The aim of this paper is to illustrate the US assessment of ankle lesions in patients with inflammatory rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus, focusing on the utility of PDUS.

  13. IBD5 polymorphisms in inflammatory bowel disease: Association with response to infliximab

    Institute of Scientific and Technical Information of China (English)

    Elena Urcelay; Juan Luis Mendoza; Alfonso Martínez; Laura Fernández; Carlos Taxonera; Manuel Díaz-Rubio; Emilio G.de la Concha

    2005-01-01

    AIM: Inflammatory bowel diseases (IBD) are multifactorial pathologies of unknown etiology. One susceptibility locus,IBD5, has been mapped to chromosome 5q31. We analyzed our Spanish cohorts of Crohn's disease (CD)and ulcerative colitis (UC) patients to determine whether this locus is associated with IBD, and to ascertain the main clinical phenotype influenced by this risk factor. The kind of interaction, either genetic heterogeneity or epistasis, between this IBD5 susceptibility region and the NOD2/CARD15 gene mutations was studied as well.Finally, ve assessed whether this locus can predict response to infliximab therapy.METHODS: A case control study was performed with 274CD and 211 UC patients recruited from a single center and 511 healthy ethnically matched controls. Two polymorphisms were genotyped in the IBD5 locus and three in the CARD15/NOD2 gene.RESULTS: Our results evidence association only with CD especially with the fistulizing phenotype and in the absence of NOD2/CARD15 variants (mutant allele frequency in patients vscontrols: OR = 2.03, 95% CI = 1.35-3.06,P<0.01). The frequency of the IBD5 homozygous mutant genotype significantly increased in CD patients lacking response to infliximab (RR = 3.88, 95% CI = 1.18-12.0,P<0.05). UC patients overall do not show association with 5q31 polymorphisms, although a similar trend to the one observed in CD is found within the worse prognosis group.CONCLUSION: The IBD5 variants may enhance an individual carrier's risk for CD, mainly in the absence of the NOD2/CARD15 mutations and in fistulizing patients.The data presented suggest the potential role of the 5q31polymorphisms as markers of response to infiiximab.

  14. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Directory of Open Access Journals (Sweden)

    Manoj K Bhasin

    Full Text Available The relaxation response (RR is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS as top upregulated critical molecules (focus hubs and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  15. Systemic Inflammatory Response and Serum Lipopolysaccharide Levels Predict Multiple Organ Failure and Death in Alcoholic Hepatitis

    Science.gov (United States)

    Michelena, Javier; Altamirano, José; Abraldes, Juan G.; Affò, Silvia; Morales-Ibanez, Oriol; Sancho-Bru, Pau; Dominguez, Marlene; García-Pagán, Juan Carlos; Fernández, Javier; Arroyo, Vicente; Ginès, Pere; Louvet, Alexandre; Mathurin, Philippe; Mehal, Wajahat Z.; Caballería, Juan; Bataller, Ramón

    2015-01-01

    Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. Conclusion In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. PMID:25761863

  16. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Science.gov (United States)

    Bhasin, Manoj K; Dusek, Jeffery A; Chang, Bei-Hung; Joseph, Marie G; Denninger, John W; Fricchione, Gregory L; Benson, Herbert; Libermann, Towia A

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  17. Arginine transport and nitric oxide production: role in the inflammatory response

    OpenAIRE

    Barilli, Amelia

    2008-01-01

    The research concerns the characterization of the pathways responsible for the recruitment of L-arginine, the obliged substrate for nitric oxide biosynthesis, in human cells. Endothelial cells and monocytes/macrophages have been employed, as the cell types more directly linked to NO pathway. As for human endothelium, only system y+ is involved in the inflammatory response: both TNFα and rapamycin, an mTOR inhibitor employed in clinical angioplasty, lead to a massive increase of CAT-mediated a...

  18. Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma.

    Science.gov (United States)

    Reghini, Maria Fernanda S; Ramires Neto, Carlos; Segabinazzi, Lorenzo G; Castro Chaves, Maria Manoela B; Dell'Aqua, Camila de Paula F; Bussiere, Maria Clara C; Dell'Aqua, José Antonio; Papa, Frederico O; Alvarenga, Marco Antonio

    2016-07-15

    Degenerative changes of the endometrium are directly related to age and fertility in mares. Chronic degenerative endometritis (CDE) is correlated with uterine fluid retention and reduced ability to clear uterine inflammation. Recent research in the areas of equine surgery and sports medicine has shown that platelet-rich plasma (PRP) treatment acts as an immunomodulator of the inflammatory response. Therefore, the aim of this study was to determine if the uterine infusion of PRP could modulate the local inflammatory response and modify the intrauterine NO concentrations after artificial insemination (AI) in both normal mares and those with CDE. Thirteen mares with endometrium classified as grade III on the histology (mares with CDE) and eight mares with endometrial histological classification I or II-a normal mares were selected to investigate the effect of PRP therapy. The mares were inseminated with fresh semen in two consecutive cycles in a crossover study design. Thereby, each mare served as its own control and the treatment was performed with intrauterine PRP infusion four hours after AI. The percentage of neutrophils in uterine cytology (CIT, %), uterine fluid accumulation observed on ultrasonography (FLU, mm) and nitric oxide concentration of uterine fluid (NO, μM) were analyzed before and 24 hours after AI. The results reported that mares with CDE (CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61) have a higher (P inflammatory response after AI than normal mares (CIT, 24.4 ± 3.56, FLU, 0), but NO concentrations did not differ (P > 0.05) between categories of mares. In treated cycles with PRP, the intrauterine inflammatory response decrease (P inflammatory response to semen in mares with CDE but did not reduce NO concentrations in intrauterine fluid.

  19. 20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

    Science.gov (United States)

    Landis, R Clive

    2015-03-01

    The "systemic inflammatory response" has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis has since been updated at a conference in 2001 advocating PIRO (Predisposition, Infection, host Response, Organ dysfunction) as a hypothetical model to better link sepsis with clinical outcome. PIRO is readily adaptable to cardiothoracic surgery and provides the precedent and road map for how to update a definition. The need is obvious since the current definition of SIRS is widely disregarded in heart surgery: a dwindling proportion (14%) of articles on the systemic inflammatory response even mention SIRS and 0% monitored SIRS criteria in the past decade in an evidence-based review of anti-inflammatory interventions. The name "inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R in PIRO) to better convey the wide spectrum of host defensive pathways activated during heart surgery (i.e., complement, coagulation, fibrinolysis, kinins, cytokines, proteases, hemolysis, oxidative stiess). A variant on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid conditions (P) and the inevitable Insult (I) from surgery, to better link risk exposures to Organ dysfunction (O) in heart surgery. The precedent of PIRO suggests the following steps will be required to redefine the systemic inflammatory response: 1) buy-in from the leading societies for cardiothoracic surgery, anesthesia, and perfusion on the need for a re-definition conference, 2) assigning relative risk scores to different

  20. Soft regulation of inflammatory immune responses%炎症免疫反应软调节

    Institute of Scientific and Technical Information of China (English)

    魏伟

    2016-01-01

    炎症反应和免疫反应在整体、组织、细胞和分子等各层次密不可分。该文提出炎症免疫反应( inflammatory immune responses, IIR)是机体炎症免疫相关细胞依据内外环境变化所表现出的适度或异常的系统反应;简述了参与IIR的炎症免疫细胞(巨噬细胞、树突细胞、T 细胞、B 细胞等及其亚型)、非炎症免疫细胞(如胶质细胞、内皮细胞、上皮细胞、成纤维细胞、滑膜细胞、肝细胞等)及细胞因子/受体信号转导的研究进展,指出了目前临床上使用的影响IIR药物存在的问题,提出炎症免疫反应软调节( soft regulation of inflammato-ry immune responses,SRIIR)是研发治疗IIR相关疾病创新药物的新方向。%Inflammation reaction and immune response are in-separable in the levels of system, tissue, cell and molecule. In-flammatory immune responses ( IIR) is proposed in this paper, which is defined a moderate or abnormal system responses of in-flammatory immune related cells in responding to the internal and external environment changes of body. It is described briefly that the research progresses of inflammatory immune cells ( e. g. , macrophages, dendritic cells, T cells and B cells, etc. ) and non-inflammatory immune cells ( e. g. , glial cells, endothe-lial cells, epithelial cells, fibroblasts, synovial cells and liver cells, etc. ) , and cytokines/receptor signal transduction in-volved in IIR. Moreover, the existing problems about regulating IIR drugs clinically are summarized. It is firstly put forward that soft regulation of inflammatory immune responses ( SRIIR) is a new direction of discovery and development of new drugs for the treatment of IIR related diseases.

  1. Training increases anabolic response and reduces inflammatory response to a single practice in elite male adolescent volleyball players.

    Science.gov (United States)

    Nemet, Dan; Portal, Shawn; Zadik, Zvi; Pilz-Burstein, Rutie; Adler-Portal, Dana; Meckel, Yoav; Eliakim, Alon

    2012-01-01

    We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Fourteen male, elite, national team-level, Israeli volleyball players (age, 16.3±1.1 years, Tanner stage 4-5) participated in the study. Blood samples were collected before and immediately after a typical 60-min volleyball practice, before and after 7 weeks of training during the initial phases of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, and testosterone; the catabolic hormone cortisol; the pro-inflammatory markers interleukin (IL) 6, and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of both anaerobic and aerobic properties. Before the training intervention, the typical volleyball practice was associated with a significant increase of GH and testosterone and also with a significant increase of IL-6. Training resulted in a significantly greater GH response (ΔGH, 2.5±2.4 vs. 4.7±3.0 ng/mL, before and after training, respectively; pvolleyball practice. The results suggest that, along with the improvement of anaerobic and aerobic characteristics, training leads to a greater anabolic and reduced inflammatory response to exercise.

  2. Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs.

    Science.gov (United States)

    Morris, Angie S; Adamcakova-Dodd, Andrea; Lehman, Sean E; Wongrakpanich, Amaraporn; Thorne, Peter S; Larsen, Sarah C; Salem, Aliasger K

    2016-01-22

    Amorphous silica nanoparticles (NPs) possess unique material properties that make them ideal for many different applications. However, the impact of these materials on human and environmental health needs to be established. We investigated nonporous silica NPs both bare and modified with amine functional groups (3-aminopropyltriethoxysilane (APTES)) in order to evaluate the effect of surface chemistry on biocompatibility. In vitro data showed there to be little to no cytotoxicity in a human lung cancer epithelial cell line (A549) for bare silica NPs and amine-functionalized NPs using doses based on both mass concentration (below 200μg/mL) and exposed total surface area (below 14m(2)/L). To assess lung inflammation, C57BL/6 mice were administered bare or amine-functionalized silica NPs via intra-tracheal instillation. Two doses (0.1 and 0.5mg NPs/mouse) were tested using the in vivo model. At the higher dose used, bare silica NPs elicited a significantly higher inflammatory response, as evidence by increased neutrophils and total protein in bronchoalveolar lavage (BAL) fluid compared to amine-functionalized NPs. From this study, we conclude that functionalization of nonporous silica NPs with APTES molecules reduces murine lung inflammation and improves the overall biocompatibility of the nanomaterial.

  3. PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses.

    Science.gov (United States)

    Uchida, Satoshi; Itaka, Keiji; Chen, Qixian; Osada, Kensuke; Ishii, Takehiko; Shibata, Masa-Aki; Harada-Shiba, Mariko; Kataoka, Kazunori

    2012-06-01

    Safety is a critical issue in clinical applications of nonviral gene delivery systems. Safe and effective gene introduction into the lungs was previously achieved using polyplexes from poly(ethyleneglycol) (PEG)-block-polycation [PEG-block-PAsp(DET)] and plasmid DNA (pDNA). Although PEGylated polyplexes appeared to be safe, an excess ratio of polycation to pDNA was needed to obtain sufficient transgene expression, which may cause toxicities shortly after gene introduction. In the present study, we investigated the combined use of two polymers, PEG-block-PAsp(DET) (B) and homo PAsp(DET) (H) across a range of mixing ratios to construct polyplexes. Although transgene expressions following in vitro transfections increased in parallel with increased proportions of H, polyplexes with B/H = 50/50 formulation produced the highest expression level following in vivo intratracheal administration. Higher proportions of H elicited high levels of cytokine induction with significant inflammation as assessed by histopathological examinations. Based on the aggregation behavior of polyplexes in bronchoalveolar lavage fluids (BALFs), we suggested that rapid aggregation of polyplexes in the lung induced acute inflammatory responses, resulting in reduced transgene expression. B/H formulation of polyplex can help to improve gene therapy for the respiratory system because it achieves both effective PEG shielding of polyplexes and functioning of PAsp(DET) polycations to enhance endosomal escape.

  4. The clinical value of the systemic inflammatory response syndrome (SIRS) in abdominal aortic aneurysm repair.

    Science.gov (United States)

    Norwood, M G; Bown, M J; Lloyd, G; Bell, P R F; Sayers, R D

    2004-03-01

    The systemic inflammatory response syndrome (SIRS) is common after major surgery. We examine the dynamics of SIRS in AAA patients, and assess the impact of the number of SIRS criteria on patient outcome. Prospective study of 151 consecutive patients with AAA, undergoing repair electively, urgently or with rupture. SIRS scores and organ failure scores were recorded prospectively each day for all patients. Outcome measures included length of stay, evidence of organ failure and mortality. The majority of patients developed SIRS postoperatively. Elective patients with a cumulative SIRS score of > or =10 during postoperative days 1-4 were more likely to die, compared to patients with a SIRS score of SIRS late in the postoperative period (day 5-10) was associated with adverse outcome (death) in elective patients (p=0.01). The actual number of SIRS criteria present did not significantly correlate with either outcome or the incidence of organ failure. SIRS is common in patients undergoing AAA repair. The SIRS score provides useful information regarding a patient's physiological state. High SIRS scores, and the development of SIRS late in the postoperative period are associated with adverse outcome in elective patients, and can therefore be used as an indicator of potential problems.

  5. Preoperative nutritional status predicts the severity of the systemic inflammatory response syndrome (SIRS) following major vascular surgery.

    Science.gov (United States)

    Hassen, T A; Pearson, S; Cowled, P A; Fitridge, R A

    2007-06-01

    This study examined the relationship between pre-operative nutritional status and systemic inflammatory response syndrome (SIRS) or sepsis following major vascular surgery. Subjects undergoing open AAA repair, EVAR or lower limb revascularisation were studied prospectively. Pre-operative nutrition was assessed clinically using Mini-Nutritional Assessment (MNA) and body composition was measured by dual energy X-ray absorptiometry (DEXA) scanning. SIRS severity was assessed for 5 post-operative days and sepsis noted within 30 days of surgery. Using MNA, neither SIRS severity nor sepsis occurrence differed significantly between 'well-nourished' subjects and those 'at risk of malnutrition'. Using DEXA, negative associations existed between body mass index and both SIRS score and SIRS duration. Fat free mass (FFM) was negatively associated with SIRS score and duration. Negative associations also existed between skeletal muscle mass (SMM) and SIRS score and duration. SMM was also negatively correlated with post-operative length of stay in hospital. There were no significant correlations between sepsis and any nutritional indices. Lower pre-operative nutritional indices, indicating protein energy malnutrition, were associated with more severe systemic inflammatory responses following major vascular surgery.

  6. The HMGB1 signaling pathway activates the inflammatory response in Schwann cells.

    Science.gov (United States)

    Man, Li-Li; Liu, Fan; Wang, Ying-Jie; Song, Hong-Hua; Xu, Hong-Bo; Zhu, Zi-Wen; Zhang, Qing; Wang, Yong-Jun

    2015-10-01

    Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1 (HMGB1), is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schw-ann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products (RAGE), but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

  7. Beneficial Effects of Fractions of Nardostachys jatamansi on Lipopolysaccharide-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Gi-Sang Bae

    2014-01-01

    Full Text Available It has been previously shown that Nardostachys jatamansi (NJ exhibits anti-inflammatory properties against lipopolysaccharide (LPS challenges. However, the potency of NJ constituents against LPS-induced inflammatory responses has not been examined. In this present study, we determined which NJ extract fractions exhibit inhibitory effects against LPS-induced inflammatory responses. Among the NJ fractions, NJ-1, NJ-3, NJ-4, and NJ-6 inhibited LPS-induced production of NO. The NJ-3, NJ-4, and NJ-6 fractions also inhibited the production of cytokines, such as IL-1β, IL-6, and TNF-α. However, NJ-1, NJ-3, NJ-4, and NJ-6 showed differential inhibitory mechanisms against LPS-induced inflammatory responses. NJ-1, NJ-3, and NJ-4 inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK and p38 but did not affect activation of extracellular signal-regulated kinase (ERK or NF-κB. On the other hand, NJ-6 inhibited activation of MAPKs and NF-κB. In addition, in vivo experiments revealed that administration of NJ-1, NJ-3, NJ-4, and NJ-6 reduced LPS-induced endotoxin shock, with NJ-6 especially showing a marked protective effect. Taken together, these results provide the evidence for the potential of selective NJ fractions against LPS-induced inflammation. Thus, it will be advantageous to further isolate and determine single effective compounds from these potent fractions.

  8. The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

    Directory of Open Access Journals (Sweden)

    Y Vodovotz

    2009-01-01

    Full Text Available Traumatic injury/hemorrhagic shock (T/HS elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI. Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherentlydetrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partiallypropagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP’s.DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and nonhumanprimates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS andTBI in the near future.

  9. Inflammatory response of a prostate stromal cell line induced by Trichomonas vaginalis.

    Science.gov (United States)

    Im, S J; Han, I H; Kim, J H; Gu, N Y; Seo, M Y; Chung, Y H; Ryu, J S

    2016-04-01

    While Trichomonas vaginalis, a cause of sexually transmitted infection, is known as a surface-dwelling protozoa, trichomonads have been detected in prostatic tissue from benign prostatic hyperplasia and prostatitis by immunoperoxidase assay or PCR. However, the immune response of prostate stromal cells infected with T. vaginalis has not been investigated. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate stromal cells. Incubation of a human prostate stromal myofibroblast cells (WPMY-1) with live T. vaginalis T016 increased expression of the inflammatory chemokines CXCL8 and CCL2. In addition, TLR4, ROS, MAPK and NF-κB expression increased, while inhibitors of TLR4, ROS, MAPKs and NF-κB reduced CXCL8 and CCL2 production. Medium conditioned by incubation of WPMY-1 cells with T. vaginalis stimulated the migration of human neutrophils and monocytes (THP-1 cells). We conclude that T. vaginalis increases CXCL8 and CCL2 production by human prostate stromal cells by activating TLR4, ROS, MAPKs and NF-κB, and this in turn attracts neutrophils and monocytes and leads to an inflammatory response. This study is the first attempt to demonstrate an inflammatory reaction in prostate stromal cells caused by T. vaginalis.

  10. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  11. Human colon carcinogenesis is associated with increased interleukin-17-driven inflammatory responses

    Directory of Open Access Journals (Sweden)

    Xie Z

    2015-03-01

    Full Text Available Zhaohui Xie,1 Yine Qu,2 Yanli Leng,2 Wenxiu Sun,2 Siqi Ma,2 Jingbo Wei,2 Jiangong Hu,3 Xiaolan Zhang1 1Department of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Histology and Embryology, Hebei United University School of Basic Medicine, Tangshan, Hebei, People’s Republic of China; 3Department of Pathology, the Second Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China Abstract: Inflammation is known to contribute to carcinogenesis in human colorectal cancer. Proinflammatory cytokine interleukin-17 (IL-17 or IL-17A has been shown to play a critical role in colon carcinogenesis in mouse models. However, few studies have investigated IL-17A in human colon tissues. In the present study, we assessed IL-17-driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human colon polyps diagnosed as benign adenomas. We found that human colon adenocarcinomas contained the highest levels of IL-17A cytokine, which was significantly higher than the IL-17A levels in the adenomas, ulcerative colitis, and normal colon tissues (P<0.01. The levels of IL-17 receptor A (IL-17RA were also the highest in human colon adenocarcinomas, followed by adenomas and ulcerative colitis. The increased levels of IL-17A and IL-17RA were accompanied with increased IL-17-driven inflammatory responses, including activation of extracellular signal-regulated kinase (ERK1/2 and c-Jun N-terminal kinase (JNK pathways, increase in expression of matrix metalloproteinase (MMP9, MMP7, MMP2, B-cell lymphoma (Bcl-2, and cyclin D1, decrease in Bcl-2-associated X protein (BAX expression, and increase in vascular endothelial growth factor (VEGF and VEGF receptor (VEGFR expression that

  12. Cardiac abnormalities assessed by non-invasive techniques in patients with newly diagnosed idiopathic inflammatory myopathies

    DEFF Research Database (Denmark)

    Diederichsen, Louise Pyndt; Simonsen, Jane Angel; Diederichsen, Axel Cosmus Pyndt

    2015-01-01

    inflammatory myopathies (IIM) by means of non-invasive techniques. METHODS: Fourteen patients with IIM (8 polymyositis, 4 dermatomyositis, 2 cancer-associated dermatomyositis) and 14 gender- and age- matched healthy control subjects were investigated. Participant assessments included a cardiac questionnaire...

  13. Effects of Thymol and Carvacrol, Constituents of Thymus vulgaris L. Essential Oil, on the Inflammatory Response.

    Science.gov (United States)

    Fachini-Queiroz, Fernanda Carolina; Kummer, Raquel; Estevão-Silva, Camila Fernanda; Carvalho, Maria Dalva de Barros; Cunha, Joice Maria; Grespan, Renata; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2012-01-01

    Thyme (Thymus vulgaris L., Lamiaceae) is an aromatic and medicinal plant that has been used in folk medicine, phytopharmaceutical preparations, food preservatives, and as an aromatic ingredient. The effect of Thymus vulgaris essential oil (TEO) and its isolated constituents thymol and cavacrol (CVL) were studied in the following experimental models: ear edema, carrageenan-induced pleurisy, and chemotaxis in vitro. In the pleurisy model, TEO, CVL, and thymol significantly inhibited inflammatory edema. However, only TEO and CVL inhibited leukocyte migration. In the in vitro chemotaxis experiment, CVL inhibited leukocyte migration, whereas thymol exerted a potent chemoattractant effect. In the ear edema model, CVL (10 mg/ear), applied topically, reduced edema formation, exerting a topical anti-inflammatory effect. Thymol did not reduce edema formation but rather presented an irritative response, probably dependent on histamine and prostanoid release. Our data suggest that the antiinflammatory effects of TEO and CVL are attributable to the inhibition of inflammatory edema and leukocyte migration.

  14. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  15. High-intensity interval training induces a modest systemic inflammatory response in active, young men

    Directory of Open Access Journals (Sweden)

    Zwetsloot KA

    2014-01-01

    Full Text Available Kevin A Zwetsloot,1 Casey S John,1 Marcus M Lawrence,1 Rebecca A Battista,1 R Andrew Shanely1,2 1Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC, USA; 2Human Performance Laboratory, North Carolina Research Campus, Appalachian State University, Kannapolis, NC, USA Abstract: The purpose of this study was to determine: 1 the extent to which an acute session of high-intensity interval training (HIIT increases systemic inflammatory cytokines and chemokines, and 2 whether 2 weeks of HIIT training alters the inflammatory response. Eight recreationally active males (aged 22±2 years performed 2 weeks of HIIT on a cycle ergometer (six HIIT sessions at 8–12 intervals; 60-second intervals, 75-second active rest at a power output equivalent to 100% of their predetermined peak oxygen uptake (VO2max. Serum samples were collected during the first and sixth HIIT sessions at rest and immediately, 15, 30, and 45 minutes post-exercise. An acute session of HIIT induced significant increases in interleukin (IL-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein-1 compared with rest. The concentrations of interferon-γ, granulocyte macrophage-colony-stimulating factor, and IL-1β were unaltered with an acute session of HIIT. Two weeks of training did not alter the inflammatory response to an acute bout of HIIT exercise. Maximal power achieved during a VO2max test significantly increased 4.6%, despite no improvements in VO2max after 2 weeks of HIIT. These data suggest that HIIT exercise induces a small inflammatory response in young, recreationally active men; however, 2 weeks of HIIT does not alter this response. Keywords: cycle ergometer, inflammatory cytokines, exercise training

  16. Leptospira interrogans induces uterine inflammatory responses and abnormal expression of extracellular matrix proteins in dogs.

    Science.gov (United States)

    Wang, Wei; Gao, Xuejiao; Guo, Mengyao; Zhang, Wenlong; Song, Xiaojing; Wang, Tiancheng; Zhang, Zecai; Jiang, Haichao; Cao, Yongguo; Zhang, Naisheng

    2014-10-01

    Leptospira interrogans (L. interrogans), a worldwide zoonosis, infect humans and animals. In dogs, four syndromes caused by leptospirosis have been identified: icteric, hemorrhagic, uremic (Stuttgart disease) and reproductive (abortion and premature or weak pups), and also it caused inflammation. Extracellular matrix (ECM) is a complex mixture of matrix molecules that is crucial to the reproduction. Both inflammatory response and ECM are closed relative to reproductive. The aim of this study was to clarify how L. interrogans affected the uterus of dogs, by focusing on the inflammatory responses, and ECM expression in dogs uterine tissue infected by L. interrogans. In the present study, 27 dogs were divided into 3 groups, intrauterine infusion with L. interrogans, to make uterine infection, sterile EMJH, and normal saline as a control, respectively. The uteruses were removed by surgical operation in 10, 20, and 30 days, respectively. The methods of histopathological analysis, ELISA, Western blot and qPCR were used. The results showed that L. interrogans induced significantly inflammatory responses, which were characterized by inflammatory cellular infiltration and high expression levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in uterine tissue of these dogs. Furthermore, L. interrogans strongly down-regulated the expression of ECM (collagens (CL) IV, fibronectins (FN) and laminins (LN)) in mRNA and protein levels. These data indicated that strongly inflammatory responses, and abnormal regulation of ECM might contribute to the proliferation of dogs infected by L. interrogans.

  17. Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement.

    Directory of Open Access Journals (Sweden)

    Gabor Erdoes

    Full Text Available To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR or transcatheter aortic valve implantation (TAVI with different technical approaches.Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47 or minimized extracorporeal circulation (MECC, n = 15, or TAVI using either transapical (TA, n = 15 or transfemoral (TF, n = 24 access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL-6, IL-8, IL-10, human leukocyte antigen (HLA-DR, white blood cell count, high-sensitivity C-reactive protein (hs-CRP and soluble L-selectin (sCD62L levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison as determined by the Greenhouse-Geisser correction.SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively. SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001 in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017. Significantly smaller changes in the inflammatory markers were observed in TF-TAVI.Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not

  18. Inflammatory and regenerative responses in salmonids following mechanical tissue damage and natural infection

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Lunder, Tor; Nielsen, Michael Engelbrecht

    2010-01-01

    Locale responses in muscle tissue against either a sterile tissue damage or infection were compared in salmonid fish in order to examine the inflammatory responses and regeneration of tissue. From higher vertebrates both damage and infection are known to cause inflammation since DAMPs released from...... injured cells as well as PAMPs from the surface of pathogens are immunogenic. To examine this in salmonid fishes, Atlantic salmon (Salmo salar) were infected with Moritella viscosus, the causative agent of winter ulcer. Muscle tissue was sampled from infected fish at 4, 7 and 14 days post infection...... are coding for immunological factors and tissue regeneration. Locale, inflammatory responses were seen as strong up-regulation of IL-1β and IL-8 in both groups of fish, but it was more pronounced in infected fish. Expression of the toll-like receptors showed induction of TLR-5m following infection, but TLR-9...

  19. Modulation of inflammatory responses by diterpene acids from Helianthus annuus L.

    Science.gov (United States)

    Díaz-Viciedo, Rodrigo; Hortelano, Sonsoles; Girón, Natalia; Massó, Jose M; Rodriguez, Benjamín; Villar, Angel; de Las Heras, Beatriz

    2008-05-02

    Fractionation of a petroleum ether extract of Helianthus annuus L. led to the isolation of three diterpene acids: grandiflorolic, kaurenoic and trachylobanoic acids. These compounds were studied for potential anti-inflammatory activity on the generation of inflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. At non-toxic concentrations, these compounds reduced, in a concentration-dependent manner nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) production, as well as expression of inducible nitric oxide synthase (NOS-2) and cyclooxygenase-2 (COX-2). All diterpenoids displayed significant in vivo anti-inflammatory activity and suppressed the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mouse ear edema. In addition, inhibition of myeloperoxidase (MPO) activity, an index of cellular infiltration, was observed. In summary, our results suggest that the inhibition of the expression of NOS-2, COX-2 and the release of inflammatory cytokines, is responsible for the anti-inflammatory effects of the diterpenoids isolated from H. annuus L. which likely contributes to the pharmacological action of sunflower.

  20. GBA2-encoded β-glucosidase activity is involved in the inflammatory response to Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Nicoletta Loberto

    Full Text Available Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of β-glucosidase 2 (GBA2, has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxypentyl-deoxynojirimycin (Genz-529648. In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2.

  1. Avian leukosis virus subgroup J triggers caspase-1-mediated inflammatory response in chick livers.

    Science.gov (United States)

    Liu, Xue-lan; Shan, Wen-jie; Jia, Li-juan; Yang, Xu; Zhang, Jin-jing; Wu, Ya-rong; Xu, Fa-zhi; Li, Jin-nian

    2016-04-02

    Many pathogens trigger caspase-1-mediated innate immune responses. Avian leukosis virus subgroup J (ALV-J) causes serious immunosuppression and diverse tumors in chicks. The caspase-1 inflammasome mechanism of response to ALV-J invading remains unclear. Here we investigated the expression of caspase-1, the inflammasome adaptor NLRP3, IL-1β and IL-18 in response to ALV-J infection in the liver of chick. We found caspase-1 mRNA expression was elevated at 5 dpi and peaked at 7 dpi in ALV-J infected animals. Corresponding to this, the expressions of NLRP3 and proinflammatory cytokines IL-1β and IL-18 were significantly increased at 5 or 7 dpi. In addition, caspase-1 protein expression and inflammatory cell infiltration were induced after virus infection. These results indicated that ALV-J infection could trigger the caspase-1- mediated inflammatory response in chicks. Thus, an understanding of the inflammatory responses can provide a better insight into the pathogenicity of ALV-J and a possible anti-virus target for ALV-J infection.

  2. Fasciola hepatica Kunitz type molecule decreases dendritic cell activation and their ability to induce inflammatory responses.

    Directory of Open Access Journals (Sweden)

    Cristian R Falcón

    Full Text Available The complete repertoire of proteins with immunomodulatory activity in Fasciola hepatica (Fh has not yet been fully described. Here, we demonstrated that Fh total extract (TE reduced LPS-induced DC maturation, and the DC ability to induce allogeneic responses. After TE fractionating, a fraction lower than 10 kDa (F<10 kDa was able to maintain the TE properties to modulate the DC pro- and anti-inflammatory cytokine production induced by LPS. In addition, TE or F<10 kDa treatment decreased the ability of immature DC to stimulate the allogeneic responses and induced a novo allogeneic CD4+CD25+Foxp3+ T cells. In contrast, treatment of DC with T/L or F<10 kDa plus LPS (F<10/L induced a regulatory IL-27 dependent mechanism that diminished the proliferative and Th1 and Th17 allogeneic responses. Finally, we showed that a Kunitz type molecule (Fh-KTM, present in F<10 kDa, was responsible for suppressing pro-inflammatory cytokine production in LPS-activated DC, by printing tolerogenic features on DC that impaired their ability to induce inflammatory responses. These results suggest a modulatory role for this protein, which may be involved in the immune evasion mechanisms of the parasite.

  3. A self-assessed questionnaire can help in the diagnosis of pelvic inflammatory disease.

    Science.gov (United States)

    Bouquier, Julie; Huchon, Cyrille; Panel, Pierre; Fauconnier, Arnaud

    2014-09-01

    Pelvic inflammatory disease (PID) is often responsible for acute pelvic pain, yet its clinical diagnosis is difficult. The aim of this study was to develop and validate prediction rules for the diagnosis of PID in patients seen for acute pelvic pain, based solely on a self-assessed questionnaire. From September 2006 to April 2008, 499 consecutive patients presenting at the gynecology emergency departments of 5 hospitals for acute pelvic pain completed a Self-Assessment Questionnaire for Gynecological Emergencies. Seventy-three were identified as having a PID. Two-thirds of the database was randomly selected for the derivation of the prediction rules, and the other third was used for internal validation. We developed 2 scores, one that rules out a diagnosis of PID and one that predicts PID, based on multiple logistic regression with jackknife estimates. These scores were then validated with the validation data set. Four variables were independently associated with PID: scattered pain radiation and/or diffuse pain, insidious pain, peritoneal irritation, and abnormal vaginal discharge. They were used to create a sensitive prediction model that rules out PID. Four other variables were used to build another model that predicted PID with high specificity: abnormal vaginal discharge, bilateral pelvic pain, constipation, and presence of an intrauterine device. The probability of PID for the patients in the low-risk group was 1.1% (95% confidence interval, 0.03-5.8), and the probability of PID in the high-risk group was 55% (95% confidence interval, 31.5-76.9). These 2 prediction rules that classify patients in low risk or high risk of PID, based on simple items collected by a self-assessed questionnaire that are composed only of case history and autodescription of the pain, may prove useful for diagnosing or ruling out PID in patients with acute pelvic pain.

  4. Wild skylarks seasonally modulate energy budgets but maintain energetically costly inflammatory immune responses throughout the annual cycle

    NARCIS (Netherlands)

    Hegemann, A.; Matson, K.D.; Versteegh, M.A.; Tieleman, B.I.

    2012-01-01

    A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase res

  5. Wild Skylarks Seasonally Modulate Energy Budgets but Maintain Energetically Costly Inflammatory Immune Responses throughout the Annual Cycle

    NARCIS (Netherlands)

    Hegemann, Arne; Matson, Kevin D.; Versteegh, Maaike A.; Tieleman, B. Irene

    2012-01-01

    A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase res

  6. Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis.

    Science.gov (United States)

    Rimessi, Alessandro; Bezzerri, Valentino; Patergnani, Simone; Marchi, Saverio; Cabrini, Giulio; Pinton, Paolo

    2015-02-04

    The common pathological manifestation of cystic fibrosis (CF) is associated with an excessive lung inflammatory response characterized by interleukin-1β accumulation. CF airway epithelial cells show an exacerbated pro-inflammatory response to Pseudomonas aeruginosa; however, it is unclear whether this heightened inflammatory response is intrinsic to cells lacking CF transmembrane conductance regulator (CFTR). Here we demonstrate that the degree and quality of the inflammatory response in CF are supported by P. aeruginosa-dependent mitochondrial perturbation, in which flagellin is the inducer and mitochondrial Ca(2+) uniporter (MCU) is a signal-integrating organelle member for NLRP3 activation and IL-1β and IL-18 processing. Our work elucidates the regulation of the NLRP3 inflammasome by mitochondrial Ca(2+) in the P. aeruginosa-dependent inflammatory response and deepens our understanding of the significance of mitochondria in the Ca(2+)-dependent control of inflammation.

  7. α1-Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses

    Science.gov (United States)

    Geraghty, Patrick; Eden, Edward; Pillai, Manju; Campos, Michael; McElvaney, Noel G.

    2014-01-01

    Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease. Objectives: Given their common effects, this study investigated whether A1AT acts via PP2A to alter tumor necrosis factor (TNF) signaling, inflammation, and proteolytic responses in this disease. Methods: PP2A activity was measured in peripheral blood neutrophils from A1AT-deficient (PiZZ) and healthy (PiMM) individuals and in alveolar macrophages from normal (60 mg/kg) and high-dose (120 mg/kg) A1AT-treated PiZZ subjects. PP2A activation was assessed in human neutrophils, airway epithelial cells, and peripheral blood monocytes treated with plasma purified A1AT protein. Similarly, lung PP2A activity was measured in mice administered intranasal A1AT. PP2A was silenced in lung epithelial cells treated with A1AT and matrix metalloproteinase and cytokine production was then measured following TNF-α stimulation. Measurements and Main Results: PP2A was significantly lower in neutrophils isolated from PiZZ compared with PiMM subjects. A1AT protein activated PP2A in human alveolar macrophages, monocytes, neutrophils, airway epithelial cells, and in mouse lungs. This activation required functionally active A1AT protein and protein tyrosine phosphatase 1B expression. A1AT treatment acted via PP2A to prevent p38 and IκBα phosphorylation and matrix metalloproteinase and cytokine induction in TNF-α–stimulated epithelial cells. Conclusions: Together, these data indicate that A1AT modulates PP2A to counter inflammatory and proteolytic responses induced by TNF signaling in the lung. PMID:25341065

  8. Response of Iron Deficiency Anemia to Intravenous Iron Sucrose in Pediatric Inflammatory Bowel Disease

    Science.gov (United States)

    2016-01-01

    OBJECTIVES: The objective of this retrospective study was to evaluate the safety and efficacy of intravenous iron sucrose (IS) in iron deficient children with inflammatory bowel disease (IBD) in remission. METHODS: Electronic medical records at a university based pediatric children's hospital were searched for patients in age range 0 to 18 years with diagnosis of IBD and treatment with IS over a 1-year period. Response to IS treatment was assessed by posttreatment changes in ferritin, hemoglobin (Hb), and mean corpuscular volume (MCV). Patients with recorded symptoms of active disease were excluded from analysis of treatment response. RESULTS: Twelve patients were identified by the search criteria, 10 with Crohn's disease (CD), 2 with ulcerative colitis (UC). Data represent 8 patients in remission, 7 with CD and 1 with UC, who received a total of 34 IS infusions. Iron sucrose was administered in cycles of 2 infusions, 2.5 to 3.5 mg/kg/dose (maximum 200 mg), 1 week apart. Mean ferritin increased from 21.4 ± 9.2 to 52.9 ± 10.1 ng/mL (p = 0.0005), Hb from 10.9 ± 0.4 to 11.3 ± 0.3 g/dL (p = 0.02), and MCV from 76.9 ± 2 to 79.4 ± 2 fl (p = 0.006). Iron sucrose treatment normalized ferritin in 6 of 7, Hb in 2 of 8, and MCV in 2 of 5 patients with low pretreatment levels. No adverse effects were recorded. CONCLUSIONS: Two IS infusions of 2.5 to 3.5 mg/kg/dose (maximum 200 mg), given 1 week apart normalized ferritin levels in most pediatric IBD patients in remission without adverse effects. Further studies are needed to determine optimal dosing schedules. PMID:27199624

  9. Assessment of topical non-steroidal anti-inflammatory drugs in animal models.

    Science.gov (United States)

    Hiramatsu, Y; Akita, S; Salamin, P A; Maier, R

    1990-10-01

    Four commercial gel preparations of topical anti-inflammatory agents have been assessed in six animal models commonly used to determine the biological activity of non-steroidal anti-inflammatory agents for systemic administration. Only UV-induced erythema of the skin, adjuvant induced arthritis and the measurement of vascular permeability proved suitable for differentiation of the potency of the four topical agents. Carrageenin-induced paw oedema, the cotton pellet test and the assessment of the pain threshold according to Randall and Selitto were of little value. The effects of the gel preparation of diclofenac (CAS 15307-86-5) diethylammonium (Voltaren Emulgel) were comparable to two preparations containing 1% and 5% active ingredient, respectively. Gel 4 showed low overall activity. The experiments demonstrated that some of the models used for the assessment of anti-inflammatory agent for systemic administration proved suitable for the testing of topical preparations and that percutaneous absorption was insufficient to elicit anti-inflammatory effect in the animals at sites remote from the site of application.

  10. Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2011-12-01

    Full Text Available Abstract Background Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS production. Whey protein (WP is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN, a wounded diabetic group (WD and a wounded diabetic group orally supplemented with whey protein (WDWP at a dose of 100 mg/kg body weight. Results Whey protein was found to significantly decrease the levels of malondialdehyde (MDA, nitric oxide (NO and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1β, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. Conclusion In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines.

  11. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia.

    Science.gov (United States)

    Jung, Hyo Won; Mahesh, Ramalingam; Lee, Jong Gu; Lee, Seung Ho; Kim, Young Shik; Park, Yong-Ki

    2010-08-23

    The activation of microglia plays an important role in a variety of brain disorders by the excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokines. We investigated here whether pinoresinol isolated from the fruits of Forsythia koreana Nakai inhibits the inflammatory responses in LPS-activated microglia. Pinoresinol inhibited the production of NO, PGE(2), TNF-alpha, IL-1beta and IL-6 in LPS-activated primary microglia. Also, pinoresinol attenuated mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in LPS-activation. However, most of these inhibitory effects of pinoresinol have been mediated by extracellular-signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) phosphorylation and the NF-kappaB dependent. The results suggest that pinoresinol attenuates inflammatory responses of microglia and could be potentially useful in modulation of inflammatory status in brain disorders.

  12. Identification of a common gene expression response in different lung inflammatory diseases in rodents and macaques.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available To identify gene expression responses common to multiple pulmonary diseases we collected microarray data for acute lung inflammation models from 12 studies and used these in a meta-analysis. The data used include exposures to air pollutants; bacterial, viral, and parasitic infections; and allergic asthma models. Hierarchical clustering revealed a cluster of 383 up-regulated genes with a common response. This cluster contained five subsets, each characterized by more specific functions such as inflammatory response, interferon-induced genes, immune signaling, or cell proliferation. Of these subsets, the inflammatory response was common to all models, interferon-induced responses were more pronounced in bacterial and viral models, and a cell division response was more prominent in parasitic and allergic models. A common cluster containing 157 moderately down-regulated genes was associated with the effects of tissue damage. Responses to influenza in macaques were weaker than in mice, reflecting differences in the degree of lung inflammation and/or virus replication. The existence of a common cluster shows that in vivo lung inflammation in response to various pathogens or exposures proceeds through shared molecular mechanisms.

  13. Characterisation of inflammatory response, coagulation, and radiological findings in Katayama fever: a report of three cases at the Medical University of Vienna, Austria

    Science.gov (United States)

    2014-01-01

    Background Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection. It is predominantly reported in travellers from non-endemic regions. Whereas the immunological response to Schistosoma infection is well characterised, alterations in inflammatory markers and coagulation in response to acute infection are poorly understood. Methods Here we report the clinical, laboratory and radiological characteristics of three returning travellers with Katayama fever. Inflammatory markers and coagulation status were assessed repeatedly during follow-up to characterise the host response to infection. Radiographic findings were correlated with clinical and laboratory markers. Results Clinical symptoms were suggestive of a significant inflammatory response in all patients including high fever (>39°C), cough, and general malaise. Classical inflammatory markers including blood sedimentation rate, C-reactive protein, and serum amyloid A were only moderately elevated. Marked eosinophilia (33–42% of white blood cells) was observed and persisted despite anti-inflammatory and anthelminthic treatment for up to 32 weeks. Analysis of blood coagulation markers indicated increased coagulability reflected by elevated D-dimer values (0.57–1.17 μg/ml) and high thrombin generating potentials (peak thrombin activity: 311–384 nM). One patient showed particularly high levels of microparticle-associated tissue factor activity at initial presentation (1.64 pg/ml). Multiple pulmonary and hepatic opacities demonstrated by computed tomography (CT) scanning were associated with raised inflammatory markers in one patient. Conclusions The characterisation of the inflammatory response, blood coagulation parameters and radiological findings in three patients adds to our current understanding of Katayama fever and serves as a starting point for further systematic investigations of the pathophysiology of

  14. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Catherine B. Lawrence

    2012-09-01

    Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

  15. Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis

    Directory of Open Access Journals (Sweden)

    Yehudit eGnatek

    2012-05-01

    Full Text Available Recent studies show a key role of brain inflammation in epilepsy. However, the mechanisms controlling brain immune response are only partly understood. In the periphery, acetylcholine (ACh release by the vagus nerve restrains inflammation by inhibiting the activation of leukocytes. Recent reports suggested a similar anti-inflammatory effect for ACh in the brain. Since brain cholinergic dysfunction are documented in epileptic animals, we explored changes in brain cholinergic gene expression and associated immune response during pilocarpine-induced epileptogenesis. Levels of acetylcholinesterase (AChE and inflammatory markers were measured using real-time RT-PCR, in-situ hybridization and immunostaining in wild type (WT and transgenic mice over-expressing the "synaptic" splice variant AChE-S (TgS. One month following pilocarpine, mice were video-monitored for spontaneous seizures. To test directly the effect of ACh on the brain's innate immune response, cytokines expression levels were measured in acute brain slices treated with cholinergic agents. We report a robust upregulation of AChE as early as 48 hrs following pilocarpine-induced status epilepticus (SE. AChE was expressed in hippocampal neurons, microglia and endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed constitutive increased microglial activation, elevated levels of pro-inflammatory cytokines 48 hrs after SE and accelerated epileptogenesis compared to their WT counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine-receptor independent anti-inflammatory effect of ACh in brain slices maintained ex vivo. Our work demonstrates for the first time, that ACh directly suppresses brain innate immune response and that AChE up-regulation after SE is associated with enhanced immune response, facilitating the epileptogenic process. Our results highlight the cholinergic system as a potential new target for the prevention of seizures and epilepsy.

  16. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  17. Immunoregulatory Role of B7-H1 in Chronicity of Inflammatory Responses

    Institute of Scientific and Technical Information of China (English)

    Haidong Dong; Xianming Chen

    2006-01-01

    Pathogenesis of most chronic human diseases, including chronic infections, autoimmune diseases and cancers, often involves a persistent, unresolved inflammatory response. The molecular mechanisms that determine the conversion of an acute inflammatory response into a chronic process had puzzled researchers for many years. Recent studies reveal that B7-H1 (CD274, PD-L1), a newly identified co-stimulatory molecule, possesses dual functions of co-stimulation of naive T cells and inhibition of activated effector T cells. The aberrant cellular expression and deregulated function of B7-H1 have been reported during chronic viral and intracellular bacterial infection, as well as in many autoimmune diseases and cancers. Importantly, the deregulation of B7-H1's dual functions appears to be associated with a prolonged and incomplete immune response by luring naive T cells for activation and dampening activated effector T cells. Moreover, development of strategies targeting B7-H1 signals provides a new and promising approach to manipulate the devastating diseases associated with chronic inflammation. Thus,B7-H1 may play a critical immunoregulatory role in the chronicity of inflammatory responses.

  18. Global analysis of neutrophil responses to Neisseria gonorrhoeae reveals a self-propagating inflammatory program.

    Directory of Open Access Journals (Sweden)

    Anna Sintsova

    2014-09-01

    Full Text Available An overwhelming neutrophil-driven response causes both acute symptoms and the lasting sequelae that result from infection with Neisseria gonorrhoeae. Neutrophils undergo an aggressive opsonin-independent response to N. gonorrhoeae, driven by the innate decoy receptor CEACAM3. CEACAM3 is exclusively expressed by human neutrophils, and drives a potent binding, phagocytic engulfment and oxidative killing of Opa-expressing bacteria. In this study, we sought to explore the contribution of neutrophils to the pathogenic inflammatory process that typifies gonorrhea. Genome-wide microarray and biochemical profiling of gonococcal-infected neutrophils revealed that CEACAM3 engagement triggers a Syk-, PKCδ- and Tak1-dependent signaling cascade that results in the activation of an NF-κB-dependent transcriptional response, with consequent production of pro-inflammatory cytokines. Using an in vivo model of N. gonorrhoeae infection, we show that human CEACAM-expressing neutrophils have heightened migration toward the site of the infection where they may be further activated upon Opa-dependent binding. Together, this study establishes that the role of CEACAM3 is not restricted to the direct opsonin-independent killing by neutrophils, since it also drives the vigorous inflammatory response that typifies gonorrhea. By carrying the potential to mobilize increasing numbers of neutrophils, CEACAM3 thereby represents the tipping point between protective and pathogenic outcomes of N. gonorrhoeae infection.

  19. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state?

    Science.gov (United States)

    Giannoudis, Peter V; Harwood, Paul John; Loughenbury, Peter; Van Griensven, Martijn; Krettek, Christian; Pape, Hans-Christoph

    2008-09-01

    Recently, increasing emphasis is being placed upon assessment of the inflammatory status of the patient. Serum inflammatory cytokines, particularly IL-6, have been used as an adjunct to this assessment. Another method uses a combination of simple laboratory and clinical data to provide an assessment of the patient's current level of systemic inflammation, the SIRS. The aim of this study was to investigate, in a group of adult trauma patients, the relationship between the interleukin-6 (IL-6) concentration, the systemic inflammatory response score (SIRS) and outcome. In patients with femoral shaft fracture, serum IL-6 levels and clinical parameters were recorded prospectively on admission and on days 1, 3, 5, and 7. Clinical course, the SIRS score and complications were documented. Nonparametric tests were used to assess relationships between variables and receiver operator characteristic (ROC) curves were used to examine their predictive values. Significance was assumed at the p SIRS state" detected early (day 1 and 3) positively correlated with the IL-6 measurement from the same period (p SIRS state (p SIRS state with an 83% sensitivity and a 75% specificity (area under ROC curve 0.76, p SIRS state and an IL-6 > 300 pg/mL was associated with a significantly increased risk of complication (pneumonia, MOF, death). Both systems were found to be significantly diagnostic of these complications using ROC curve analysis. The IL-6 concentration and SIRS score are useful adjuncts to clinical evaluation of the injured patient. In the early phase, they are closely correlated with the NISS and each other. A cutoff value of 200 pg/dL was shown to be significantly diagnostic of a SIRS state. Significant correlations between adverse events and both the IL-6 level and SIRS state are demonstrated.

  20. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2016-01-01

    Full Text Available Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8 is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

  1. Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases.

    Science.gov (United States)

    Yi, Young-Su

    2016-01-01

    Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

  2. Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response

    Science.gov (United States)

    Totsuka, Yukari; Ishino, Kousuke; Kato, Tatsuya; Goto, Sumio; Tada, Yukie; Nakae, Dai; Watanabe, Masatoshi; Wakabayashi, Keiji

    2014-01-01

    Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

  3. Lactobacillus crispatus M206119 exacerbates murine DSS-colitis by interfering with inflammatory responses

    Institute of Scientific and Technical Information of China (English)

    Fu-Xi Zhou; Lu Chen; Xiao-Wei Liu; Chun-Hui Ouyang; Xiao-Ping Wu; Xue-Hong Wang; Chun-Lian Wang

    2012-01-01

    AIM:To investigate the role of Lactobacillus crispatus (L.crispatus) strain China Center for Type Culture Collection (CCTCC) M206119 in intestinal inflammation.METHODS:Forty 8-wk-old Balb/c mice (20 ± 2 g)were divided into four groups of 10 mice each.Three groups that had received dextran sulfate sodium (DSS)were administered normal saline,sulfasalazine or CCTCC M206119 strain,and the fourth group received none of these.We assessed the severity of colitis using a disease activity index,measured the colon length and weight,collected stools and mesenteric lymph nodes for bacterial microflora analysis.One centimeter of the proximal colon,middle colon and distal colon were collected and fixed in 10% buffered formalin,dehydrated in ethanol,and embedded in paraffin.Interleukin (IL)-1β,IL-6 and tumor necrosis factor (TNF)-α expression was detected using reverse transcription polymerase chain reaction.Protective factors zonula occludens (ZO)-1 and β-defensin 2 were detected by immunoblotting.The features of CCTCC M206119 strain were identified based on morphology,biochemical profile,and 16S RNA sequencing.RESULTS:DSS-colitis animals treated with CCTCC M206119 had markedly more severe disease,with greater weight loss,diarrhea,fecal bleeding,and shortened colon length.In addition,the CCTCC-M206119-treated group had comparatively higher histological scores and more neutrophil infiltration than the controls.Expression of protective factors ZO-1 and β-defensin 2 was downregulated due to destruction of the mucosal barrier after CCTCC M206119 strain treatment.An in vitro assay demonstrated that CCTCC M206119 strain increased the nuclear translocation of nuclear factor-κB in epithelial cells.Intestinal proinflammatory or anti-inflammatory cytokine responses were evaluated.Proinflammatory colonic cytokine (IL-1β,IL-6and TNF-α) levels were clearly increased in CCTCC-M206119-treated animals,whereas anti-inflammatory colonic cytokine (IL-10) level was lowered compared with

  4. Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Yukari Totsuka

    2014-03-01

    Full Text Available Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS. Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

  5. Strategies for modulating the inflammatory response after decompression from abdominal compartment syndrome

    Science.gov (United States)

    2012-01-01

    Background Management of the open abdomen is an increasingly common part of surgical practice. The purpose of this review is to examine the scientific background for the use of temporary abdominal closure (TAC) in the open abdomen as a way to modulate the local and systemic inflammatory response, with an emphasis on decompression after abdominal compartment syndrome (ACS). Methods A review of the relevant English language literature was conducted. Priority was placed on articles published within the last 5 years. Results/Conclusion Recent data from our group and others have begun to lay the foundation for the concept of TAC as a method to modulate the local and/or systemic inflammatory response in patients with an open abdomen resulting from ACS. PMID:22472164

  6. Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Yanyan Yang

    2014-01-01

    Full Text Available Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α and cyclooxygenase-2 (COX-2. p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

  7. Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyun Sook [College of Medicine, East-West Medical Research Institute, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702 (Korea, Republic of); Son, Youngsook, E-mail: ysson@khu.ac.kr [Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, Seochun-dong, Kiheung-ku, Yong In 441-706 (Korea, Republic of)

    2014-10-10

    Highlights: • SP can increase IL-10 levels and reduce TNF-α and IL-17 levels in RA. • SP causes the increase in T{sub reg}, M2 macrophage, and MSCs in RA. • SP-induced immune suppression leads to the blockade of RA progression. • SP can be used as the therapeutics for autoimmune-related inflammatory diseases. - Abstract: Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-α) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-α and IL-17 levels. Mobilization of stem cells and induction of T{sub reg} and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases.

  8. Effects of propofol and isoflurane on haemodynamics and the inflammatory response in cardiopulmonary bypass surgery.

    Science.gov (United States)

    Sayed, S; Idriss, N K; Sayyedf, H G; Ashry, A A; Rafatt, D M; Mohamed, A O; Blann, A D

    2015-01-01

    Cardiopulmonary bypass (CPB) causes reperfusion injury that when most severe is clinically manifested as a systemic inflammatory response syndrome. The anaesthetic propofol may have anti-inflammatory properties that may reduce such a response. We hypothesised differing effects of propofol and isoflurane on inflammatory markers in patients having CBR Forty patients undergoing elective CPB were randomised to receive either propofol or isoflurane for maintenance of anaesthesia. CRP, IL-6, IL-8, HIF-1α (ELISA), CD11 and CD18 expression (flow cytometry), and haemoxygenase (HO-1) promoter polymorphisms (PCR/electrophoresis) were measured before anaesthetic induction, 4 hours post-CPB, and 24 hours later. There were no differences in the 4 hours changes in CRP, IL-6, IL-8 or CD18 between the two groups, but those in the propofol group had higher HIF-1α (P = 0.016) and lower CD11 expression (P = 0.026). After 24 hours, compared to the isoflurane group, the propofol group had significantly lower levels of CRP (P < 0.001), IL-6 (P < 0.001) and IL-8 (P < 0.001), with higher levels CD11 (P = 0.009) and CD18 (P = 0.002) expression. After 24 hours, patients on propofol had increased expression of shorter HO-1 GT(n) repeats than patients on isoflurane (P = 0.001). Use of propofol in CPB is associated with a less adverse inflammatory profile than is isofluorane, and an increased up-regulation of HO-1. This supports the hypothesis that propofol has anti-inflammatory activity.

  9. High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed by statin.

    Science.gov (United States)

    Nareika, A; Maldonado, A; He, L; Game, B A; Slate, E H; Sanders, J J; London, S D; Lopes-Virella, M F; Huang, Y

    2007-02-01

    It has been established that periodontal diseases are more prevalent and of greater severity in diabetic patients than in nondiabetic patients. Recent studies have underscored the role of monocytes and macrophages in periodontal tissue inflammation and destruction in diabetic patients. Although it has been shown that monocytes isolated from diabetic patients produce more inflammatory cytokines and that gingival crevicular fluid collected from diabetic patients contains higher levels of inflammatory cytokines than that obtained from nondiabetic patients, the underlying mechanisms are not well understood. U937 histiocytes cultured in medium containing either normal (5 mM) or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for 24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells were quantified using enzyme-linked immunosorbet assay and real-time polymerase chain reaction, respectively. In this study, we demonstrated that the pre-exposure of U937 histiocytes to high glucose concentrations markedly increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines and chemokines and the cellular inducible nitric oxide level compared with pre-exposure to normal glucose. Our data also showed that the increased secretion of cytokines was a result of increased mRNA expression. Furthermore, the effects of statin and peroxisome proliferators-activated receptor agonists on high glucose-enhanced secretion of cytokines were determined. The results showed that simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced cytokine release. This study has shown that high glucose concentrations and lipopolysaccharide act synergistically to stimulate the secretion of inflammatory mediators, and that statin is capable of suppressing the high glucose-boosted proinflammatory response. This study therefore delineates a novel mechanism by which hyperglycemia enhances the inflammatory responses of

  10. Cardiopulmonary Bypass induced Fever and Systemic inflammatory response syndrome in Paediatric patients: Management Strategy

    OpenAIRE

    Ghatnatti, Ravi; Teli, Anita; Bhattacharya, Shubhankar; Sengupta, Gautam

    2013-01-01

    Cardiopulmonary bypass is considered to be the common culprit for the occurrence of fever in the immediate post-operative period i.e, within 24 hours in pediatric patients. Other common causes contributing to fever are anaesthetic drugs, blood transfusions & pain. This early fever usually manifests as tachy-arrthymias in recovery room requiring interventions. This review intends to know the pathophysiology of fever and systemic inflammatory response syndrome after bypass (SIRAB) onset, pr...

  11. The Role of Hyperglycemia in Mechanisms of Exacerbated Inflammatory Responses within the Oral Cavity

    OpenAIRE

    Amir, Jamie; Waite, Matthew; Tobler, Jeffrey; Catalfamo, Dana L.; Koutouzis, Theofilos; Katz, Joseph; Wallet, Shannon M.

    2011-01-01

    Immune modulating factors are necessary for pathogen clearance, but also contribute to host tissues damage, as those seen in periodontal diseases. Many of these responses can be exacerbated by host conditions including type 2 diabetes [T2D], where toll-like receptor 4 [TLR4] and the receptor for advanced glycated end products [RAGE] play a significant role. Here we investigate causality associated with the increase in inflammatory markers observed in periodontally diseased patients with T2D u...

  12. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C., E-mail: susan.tilton@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Lee, K. Monica [Battelle Toxicology Northwest, Richland, WA 99352 (United States); Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  13. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  14. SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway.

    Science.gov (United States)

    Wang, Wei-Rong; Li, Ting-Ting; Jing, Ting; Li, Yan-Xiang; Yang, Xiao-Feng; He, Yan-Hao; Zhang, Wei; Lin, Rong; Zhang, Ji-Ye

    2017-01-01

    Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs). Cell autophagy was evaluated by fluorescence microscope and transmission electron microscopy. The expression of protein and mRNA were determined by Western blot analysis and real time-PCR. The production of cytokine was detected by ELISA. TNF-α induced autophagy and increased SIRT1 expression in VAFs. SIRT1 activator resveratrol enhanced TNF-α-induced VAF autophagy. In contrast, SIRT1 knockdown attenuated VAF autophagy. Both the Akt inhibitor MK2206 and mTOR inhibitor rapamycin further increased TNF-α-induced VAF autophagy. Furthermore, SIRT1 knockdown increased Akt phosphorylation and inhibited the autophagy in VAFs. However, MK2206 attenuated the effect of SIRT1 knockdown on VAF autophagy. In addition, ingenuity pathway analysis showed that there is a relationship between cell autophagy and inflammation. We found that SIRT1 knockdown increased the expression of NLRP3 and interleukin (IL)-6 and promoted the production of IL-1β in VAFs. Further study showed that autophagy activation decreased the expression of NLRP3 and IL-6 and inhibited the production of IL-1β, whereas autophagy inhibition increased the inflammatory response of VAFs. More importantly, our study showed that autophagy was involved in the degradation of NLRP3 through the autophagy-lysosome pathway. SIRT1 not only regulates VAF autophagy through the Akt/mTOR signaling pathway but also suppresses the inflammatory response of VAFs through autophagy. © 2017 The Author(s)Published by S. Karger AG, Basel.

  15. Ethanol Extract of Sarcodon asparatus Mitigates Inflammatory Responses in Lipopolysaccharide-Challenged Mice and Murine Macrophages.

    Science.gov (United States)

    Chung, Min-Yu; Jung, Sung Keun; Lee, Hye-Jin; Shon, Dong Hwa; Kim, Hyun-Ku

    2015-11-01

    A number of compounds isolated from mushrooms have exhibited disease-modifying effects. We sought to investigate the mechanisms responsible for the anti-inflammatory effects of an extract from the mushroom species Sarcodon asparatus (SAE). Male BALB/c mice (N=42; 6 weeks old) were randomly assigned to four treatment groups. Intraperitoneal administration of SAE significantly attenuated lipopolysaccharide (LPS)-mediated increases in alanine aminotransferase (ALT) activity. LPS also increased serum levels of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, which were dose-dependently and significantly attenuated by SAE. Correlative relationships between serum ALT activity and proinflammatory cytokines suggested that SAE-mediated suppression of liver injury was partly attributable to the attenuation of serum inflammatory responses. SAE significantly decreased hepatic NO(•) production and subsequent 3-nitrotyrosine formation, and the hepatic NO(•) production significantly correlated with serum ALT and cytokine levels, suggesting that SAE mitigates liver injury in association with inflammatory processes, likely by suppressing NO(•) production. Anti-inflammatory activity and further mechanisms of SAE were evaluated using RAW264.7 with LPS challenge. Noncytotoxic levels of SAE significantly attenuated NO(•) production in RAW264.7 cells and also markedly suppressed the expression of iNOS and other proinflammatory mediators, including COX-2 and IL-6, which were upregulated in the presence of LPS. SAE inhibited the phosphorylation of p65, an observation that occurred independently of IKKαβ-mediated IκBα phosphorylation. Collectively, our results demonstrate that SAE suppressed NO(•)-mediated inflammation by inhibiting p65 transcriptional activation without affecting IKKαβ-mediated IκBα phosphorylation. Further studies are warranted to examine the major compounds responsible for these effects and the mechanisms responsible for the p65

  16. Could pentraxin 3 be a new diagnostic marker for excessive inflammatory response in cardiac surgery?

    Science.gov (United States)

    Holubcova, Zdenka; Kunes, Pavel; Mandak, Jiri; Kolackova, Martina; Andrys, Ctirad; Krejsek, Jan; Holubec, Tomas

    2014-12-01

    The aim of this study was to compare the dynamics of two inflammatory response biomarkers pentraxin 3 (PTX3) and C-reactive protein (CRP) after cardiac surgery with particular regard to different postoperative clinical manifestation of inflammatory response. In this study, 42 patients undergoing open heart surgery with the use of cardiopulmonary bypass were included and divided in two groups according to the extent of clinical manifestation of inflammatory response: Group A (n=21)-patients with different severity of systemic inflammatory response syndrome (SIRS) and Group B (n=21)-patients with uneventful postoperative period (no SIRS). The serum levels of PTX3 and CRP were evaluated and compared at the following time points: before and at the end of surgery, 6 hours, 1st, 3rd, and 7th day after surgery. The dynamics of CRP levels were comparable between both groups and showed the classical characteristics after cardiac surgery with a peak on the 3rd postoperative day (113 vs. 132 mg/L). In contrast, the dynamics of PTX3 showed an earlier increase of serum levels with the peak on the 1st postoperative day in both groups (36.3 vs. 42.7 ng/mL). Importantly, a significant difference of PTX3 levels was found on the 3rd postoperative day (31.1 vs. 7.0 ng/mL; pSIRS (Group A). This study demonstrates considerably different dynamics of PTX3 levels after cardiac surgery in patients with SIRS and patients without SIRS, thus it may be indicative to start the appropriate therapy. Georg Thieme Verlag KG Stuttgart · New York.

  17. Soy biodiesel and petrodiesel emissions differ in size, chemical composition and stimulation of inflammatory responses in cells and animals.

    Science.gov (United States)

    Fukagawa, Naomi K; Li, Muyao; Poynter, Matthew E; Palmer, Brian C; Parker, Erin; Kasumba, John; Holmén, Britt A

    2013-01-01

    Debate about the biological effects of biodiesel exhaust emissions exists due to variation in methods of exhaust generation and biological models used to assess responses. Because studies in cells do not necessarily reflect the integrated response of a whole animal, experiments were conducted in two human cell lines representing bronchial epithelial cells and macrophages and female mice using identical particle suspensions of raw exhaust generated by a Volkswagen light-duty diesel engine using petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume). Tailpipe particle emissions measurement showed B0 generated two times more particle mass, larger ultrafine particle number distribution modes, and particles of more nonpolar organic composition than the B20 fuel. Biological assays (inflammatory mediators, oxidative stress biomarkers) demonstrated that particulate matter (PM) generated by combustion of the two fuels induced different responses in in vitro and in vivo models. Concentrations of inflammatory mediators (Interleukin-6, IL-6; Interferon-gamma-induced Protein 10, IP-10; Granulocyte-stimulating factor, G-CSF) in the medium of B20-treated cells and in bronchoalveolar lavage fluid of mice exposed to B20 were ∼20-30% higher than control or B0 PM, suggesting that addition of biodiesel to diesel fuels will reduce PM emissions but not necessarily adverse health outcomes.

  18. Resveratrol exerts no effect on inflammatory response and delayed onset muscle soreness after a marathon in male athletes.

    Science.gov (United States)

    Laupheimer, M W; Perry, M; Benton, S; Malliaras, P; Maffulli, N

    2014-01-01

    Objective We investigated whether the inflammatory response and delayed onset of muscle soreness after a marathon are altered by resveratrol, a natural polyphenolic flavonoid antioxidant. Design: Double blind placebo-controlled randomised pilot study. Setting: London Marathon. Participants: Marathon race participants Interventions: 7 healthy male athletes were randomised to receive Resveratrol (600 mg Resveratrol daily for 7 days immediately before the marathon) or a placebo. Main Outcome Measurements: Blood samples taken 48 hours before and 18–32 hours after the marathon were analysed for white blood cell count (WBC) and C-reactive protein (CRP). A VAS score was taken at the same times as the blood samples to assess delayed onset muscle soreness. Results: There were no significant differences between the two groups in terms of changes occurring between pre- and post- tests for WBC, CRP or VAS. Conclusions: There were no differences in immune response or delayed onset muscle soreness between resveratrol and placebo after a marathon. Further investigations are needed with longer treatment time and higher doses, analysing additional parameters such interleukins for a possible effect of resveratrol on the inflammatory response due to extensive exercise. To avoid a type II error, 17 subjects in each group would be required. PMID:25147765

  19. Toxicity monitoring with primary cultured hepatocytes underestimates the acetaminophen-induced inflammatory responses of the mouse liver.

    Science.gov (United States)

    Tachibana, Shinjiro; Shimomura, Akiko; Inadera, Hidekuni

    2011-01-01

    In vitro gene expression profiling with isolated hepatocytes has been used to assess the hepatotoxicity of certain chemicals because of animal welfare issues. However, whether an in vitro system can completely replace the in vivo system has yet to be elucidated in detail. Using a focused microarray established in our laboratory, we examined gene expression profiles in the mouse liver and primary cultured hepatocytes after treatment with different doses of acetaminophen, a widely used analgesic that frequently causes liver injury. The acute hepatotoxicity of acetaminophen was confirmed by showing the induction of an oxidative stress marker, heme oxygenase-1, elevated levels of serum transaminase, and histopathological findings. In vivo microarray and network analysis showed that acetaminophen treatment provoked alterations in relation to the inflammatory response, and that tumor necrosis factor-α plays a central role in related pathway alterations. By contrast, pathway analyses in in vitro isolated hepatocytes did not find such prominent changes in the inflammation-related networks compared with the in vivo situation. Thus, although in vitro gene expression profiles are useful for evaluating the direct toxicity of chemicals, indirect toxicities including inflammatory responses mediated by cell-cell interactions or secondary toxicity due to pathophysiological changes in the whole body may be overlooked. Our results indicate that the in vitro hepatotoxicity prediction system using isolated hepatocytes does not fully reflect the in vivo cellular response. An in vitro system may be appropriate, therefore, for high throughput screening to detect the direct hepatotoxicity of a test compound.

  20. Soy Biodiesel and Petrodiesel Emissions Differ in Size, Chemical Composition and Stimulation of Inflammatory Responses in Cells and Animals

    Science.gov (United States)

    Fukagawa, Naomi K.; Li, Muyao; Poynter, Matthew E.; Palmer, Brian C.; Parker, Erin; Kasumba, John; Holmén, Britt A.

    2013-01-01

    Debate about the biological effects of biodiesel exhaust emissions exists due to variation in methods of exhaust generation and biological models used to assess responses. Because studies in cells do not necessarily reflect the integrated response of a whole animal, experiments were conducted in two human cell lines representing bronchial epithelial cells and macrophages and female mice using identical particle suspensions of raw exhaust generated by a Volkswagen light-duty diesel engine using petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume). Tailpipe particle emissions measurement showed B0 generated two times more particle mass, larger ultrafine particle number distribution modes, and particles of more nonpolar organic composition than the B20 fuel. Biological assays (inflammatory mediators, oxidative stress biomarkers) demonstrated that particulate matter (PM) generated by combustion of the two fuels induced different responses in in vitro and in vivo models. Concentrations of inflammatory mediators (Interleukin-6, IL-6; Interferon-gamma-induced Protein 10, IP-10; Granulocyte-stimulating factor, G-CSF) in the medium of B20-treated cells and in bronchoalveolar lavage fluid of mice exposed to B20 were ~20–30% higher than control or B0 PM, suggesting that addition of biodiesel to diesel fuels will reduce PM emissions but not necessarily adverse health outcomes. PMID:24053625

  1. Acute-phase inflammatory response in idiopathic sudden deafness: pathogenic implications.

    Science.gov (United States)

    López-González, Miguel A; Abrante, Antonio; López-Lorente, Carmen; Gómez, Antonio; Domínguez, Emilio; Esteban, Francisco

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48-72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  2. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    Directory of Open Access Journals (Sweden)

    Miguel A. López-González

    2012-01-01

    Full Text Available The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  3. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  4. Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response.

    Science.gov (United States)

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Kanno, Emi; Suzuki, Aiko; Takagi, Naoyuki; Yamamoto, Hideki; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2017-09-23

    The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) compared with wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice compared with WT mice. Treatment with either anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

  5. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jiwoo [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of); Lee, Suyeon [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of)

    2016-06-10

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

  6. Effects of relaxation and stress on the capsaicin-induced local inflammatory response.

    Science.gov (United States)

    Lutgendorf, S; Logan, H; Kirchner, H L; Rothrock, N; Svengalis, S; Iverson, K; Lubaroff, D

    2000-01-01

    Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.

  7. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  8. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.

    Science.gov (United States)

    Lisboa, Felipe A; Bradley, Matthew J; Hueman, Matthew T; Schobel, Seth A; Gaucher, Beverly J; Styrmisdottir, Edda L; Potter, Benjamin K; Forsberg, Jonathan A; Elster, Eric A

    2017-04-01

    After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >10(5) colony forming units on quantitative bacteriology; and healing potential. We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser

  9. The role of oxidative stress and inflammatory response in the pathogenesis of mastitis in dairy cows

    Directory of Open Access Journals (Sweden)

    Nino Maćešić

    2017-01-01

    Full Text Available Mastitis is one of the most frequent diseases of dairy cows throughout the world, therefore it causes the greatest economic losses in dairy cattle industry. These losses are reflected through: reduced milk production, increased costs of medication and the other animal health services, reduced fertility, early culling of animals and the value of discarded milk. Mastitis is also important from the aspects of public health, milk processing and animal welfare. In the pathogenesis of mastitis the key role plays the innate immune response which is the first line of defence against the pathogen invasion of the udder. The innate immune response generates an inflammatory reaction which is the elementary response of an organism to the tissue trauma induced by any physical, chemical or biological causative agent, but primarily it is the protective mechanism of a vital significance which includes increased phagocytic activity, secretion of antimicrobial substances, fibrosis as well as the alterations in tissue structure of affected organ or body cavity. The release of a number of inflammatory mediators as well as reactive oxygen species (ROS is an important part of inflammatory response. In dairy cows, the metabolic challenge that occurred during the transition from dry period to early lactation may additionally increase the release of ROS which may contribute to development of oxidative stress and inflammatory response. Oxidative stress is defined as a shift in the balance from cellular oxidation-reduction reactions towards oxidation, i.e. to the state of excessive release of oxidants when their removal by antioxidants is impaired and even insufficient. During peripartum period antioxidantive status of dairy cows is seriously impaired and consequently both the oxidative stress and inflammatory response may present the predisposing factors to their higher susceptibility to intramammary infections (IMI and mastitis. This association between oxidative stress

  10. The role of oxidative stress and inflammatory response in the pathogenesis of mastitis in dairy cows

    Directory of Open Access Journals (Sweden)

    Romana Turk

    2017-04-01

    Full Text Available Mastitis is one of the most frequent diseases of dairy cows throughout the world, therefore it causes the greatest economic losses in dairy cattle industry. These losses are reflected through: reduced milk production, increased costs of medication and the other animal health services, reduced fertility, early culling of animals and the value of discarded milk. Mastitis is also important from the aspects of public health, milk processing and animal welfare. In the pathogenesis of mastitis the key role plays the innate immune response which is the first line of defence against the pathogen invasion of the udder. The innate immune response generates an inflammatory reaction which is the elementary response of an organism to the tissue trauma induced by any physical, chemical or biological causative agent, but primarily it is the protective mechanism of a vital significance which includes increased phagocytic activity, secretion of antimicrobial substances, fibrosis as well as the alterations in tissue structure of affected organ or body cavity. The release of a number of inflammatory mediators as well as reactive oxygen species (ROS is an important part of inflammatory response. In dairy cows, the metabolic challenge that occurred during the transition from dry period to early lactation may additionally increase the release of ROS which may contribute to development of oxidative stress and inflammatory response. Oxidative stress is defined as a shift in the balance from cellular oxidation-reduction reactions towards oxidation, i.e. to the state of excessive release of oxidants when their removal by antioxidants is impaired and even insufficient. During peripartum period antioxidantive status of dairy cows is seriously impaired and consequently both the oxidative stress and inflammatory response may present the predisposing factors to their higher susceptibility to intramammary infections (IMI and mastitis. This association between oxidative stress

  11. The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats.

    Science.gov (United States)

    Jiang, Shu-Kun; Zhang, Miao; Tian, Zhi-Ling; Wang, Meng; Zhao, Rui; Wang, Lin-Lin; Li, Shan-Shan; Liu, Min; Li, Jiao-Yong; Zhang, Meng-Zhou; Guan, Da-Wei

    2015-08-15

    Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]piperidine-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute lung injury in mice, which provide a new strategy for primary care of skeletal muscle injury. We investigated the effect of JZL184 on inflammation in rat muscle contusion model, and found decreased neutrophil and macrophage infiltration and pro-inflammatory cytokine expression. With extension of post-traumatic interval, myofiber regeneration was significantly hindered with increased collagen types I and ІІІ mRNAfibroblast infiltration as well as promoted fibrosis. Furthermore, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide (AM281, a selective cannabinoid CB1 receptor antagonist) and [6-iodo-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone (AM630, a selective cannabinoid CB2 receptor antagonist) treatment alleviated the anti-inflammatory effect of JZL184. Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoid CB1 and CB2 receptors.

  12. Protective effect of kaempferol on LPS plus ATP-induced inflammatory response in cardiac fibroblasts.

    Science.gov (United States)

    Tang, Xi-Lan; Liu, Jian-Xun; Dong, Wei; Li, Peng; Li, Lei; Hou, Jin-Cai; Zheng, Yong-Qiu; Lin, Cheng-Ren; Ren, Jun-Guo

    2015-02-01

    Inflammatory response is an important mechanism in the pathogenesis of cardiovascular diseases. Cardiac fibroblasts play a crucial role in cardiac inflammation and might become a potential therapeutic target in cardiovascular diseases. Kaempferol, a flavonoid commonly existing in many edible fruits, vegetables, and Chinese herbs, is well known to possess anti-inflammatory property and thus has a therapeutic potential for the treatment of inflammatory diseases. To date, the effect of kaempferol on cardiac fibroblasts inflammation is unknown. In this study, we investigated the anti-inflammatory effect of kaempferol on lipopolysaccharide (LPS) plus ATP-induced cardiac fibroblasts and explored the underlying mechanisms. Our results showed that kaempferol at concentrations of 12.5 and 25 μg/mL significantly suppressed the release of TNF-α, IL-1β, IL-6, and IL-18 and inhibited activation of NF-κB and Akt in LPS plus ATP-induced cardiac fibroblasts. These findings suggest that kaempferol attenuates cardiac fibroblast inflammation through suppression of activation of NF-κB and Akt.

  13. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish.

    Science.gov (United States)

    Hwang, Ji-Hyun; Kim, Kui-Jin; Ryu, Su-Jung; Lee, Boo-Yong

    2016-03-25

    Caffeine is a white crystalline xanthine alkaloid found in the seeds of coffee plants and leaves of the tea bush. In this study, we evaluated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo. RAW264.7 cells were treated with various concentrations of caffeine in the presence or absence of LPS. Caffeine decreased the LPS-induced inflammatory mediator, nitric oxide (NO). Caffeine treatment also reduced the expression of pro-inflammatory genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-3, IL-6 and IL-12, and decreased both IL-6 secretion and phosphorylated p38MAPK expression in LPS-treated RAW264.7 cells. Caffeine inhibited nuclear translocation of nuclear factor κB (NF-κB) via IκBα phosphorylation. In addition, caffeine inhibited LPS-induced NO production in zebrafish. These results suggest that caffeine may suppress LPS-induced inflammatory responses in RAW264.7 cells by regulating NF-κB activation and MAPK phosphorylation.

  14. Francisella Infection in Cultured Tilapia in Thailand and the Inflammatory Cytokine Response.

    Science.gov (United States)

    Jantrakajorn, Sasibha; Wongtavatchai, Janenuj

    2016-06-01

    Francisella infections developed in freshwater Nile Tilapia Oreochromis niloticus and red tilapia Oreochromis spp. farms in Thailand during 2012-2014. The diseased fish were lethargic and pale in color and showed numerous white nodules in their enlarged spleens. Histopathological examination and electron microscopy suggested that the white nodules were multifocal granulomas consisting of coccobacilli within vacuolated cells. Isolation of Francisella-like bacteria was achieved from 42 of 100 samples, while polymerase chain reaction confirmed Francisella infections in all samples. Analysis of the 16S rRNA gene from samples obtained from three different geographical culture areas revealed more than 99% similarity with F. noatunensis subsp. orientalis. The influence of Francisella infection on inflammatory cytokines was determined on splenic cells of fish intraperitoneally injected with the bacteria (0.8 × 10(5) colony-forming units per fish). Infected tilapia showed significantly greater expression of the pro-inflammatory genes interleukin-1β (IL-1β) and tumor necrotic factor-α (TNF-α) within 24 h postinjection (hpi) and for up to 96 hpi. However, down-regulation of an anti-inflammatory gene, transforming growth factor-β (TGF-β) was observed as early as 24 hpi. This investigation demonstrates that an imbalance between pro- and anti-inflammatory cytokines in response to the infection may account for the substantial number of granulomas in fish hematopoietic tissues that was found in the later stage of the disease. Received September 9, 2015; accepted December 13, 2015.

  15. Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response

    Science.gov (United States)

    Ng, Hang Pong; Jennings, Scott; Wang, Jack; Molina, Patricia E.; Nelson, Steve; Wang, Guoshun

    2017-01-01

    Acute alcohol exposure suppresses cell inflammatory response. The underlying mechanism has not been fully defined. Here we report that alcohol was able to activate glucocorticoid receptor (GR) signaling in the absence of glucocorticoids (GCs) and upregulated glucocorticoid-induced leucine zipper (gilz), a prominent GC-responsive gene. Such a non-canonical activation of GR was not blocked by mifepristone, a potent GC competitor. The proximal promoter of gilz, encompassing five GC-responsive elements (GREs), was incorporated and tested in a luciferase reporter system. Deletion and/or mutation of the GREs abrogated the promoter responsiveness to alcohol. Thus, the GR–GRE interaction transduced the alcohol action on gilz. Alcohol induced GR nuclear translocation, which was enhanced by the alcohol dehydrogenase inhibitor fomepizole, suggesting that it was alcohol, not its metabolites, that engendered the effect. Gel mobility shift assay showed that unliganded GR was able to bind GREs and such interaction withstood clinically relevant levels of alcohol. GR knockout via CRISPR/Cas9 gene targeting or GILZ depletion via small RNA interference diminished alcohol suppression of cell inflammatory response to LPS. Thus, a previously unrecognized, non-canonical GR activation of gilz is involved in alcohol modulation of cell immune response. PMID:28638383

  16. Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Hang Pong Ng

    2017-06-01

    Full Text Available Acute alcohol exposure suppresses cell inflammatory response. The underlying mechanism has not been fully defined. Here we report that alcohol was able to activate glucocorticoid receptor (GR signaling in the absence of glucocorticoids (GCs and upregulated glucocorticoid-induced leucine zipper (gilz, a prominent GC-responsive gene. Such a non-canonical activation of GR was not blocked by mifepristone, a potent GC competitor. The proximal promoter of gilz, encompassing five GC-responsive elements (GREs, was incorporated and tested in a luciferase reporter system. Deletion and/or mutation of the GREs abrogated the promoter responsiveness to alcohol. Thus, the GR–GRE interaction transduced the alcohol action on gilz. Alcohol induced GR nuclear translocation, which was enhanced by the alcohol dehydrogenase inhibitor fomepizole, suggesting that it was alcohol, not its metabolites, that engendered the effect. Gel mobility shift assay showed that unliganded GR was able to bind GREs and such interaction withstood clinically relevant levels of alcohol. GR knockout via CRISPR/Cas9 gene targeting or GILZ depletion via small RNA interference diminished alcohol suppression of cell inflammatory response to LPS. Thus, a previously unrecognized, non-canonical GR activation of gilz is involved in alcohol modulation of cell immune response.

  17. Effects of postoperative immune-enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome

    Institute of Scientific and Technical Information of China (English)

    蒋小华; 李宁; 朱维铭; 吴国豪; 全志伟; 黎介寿

    2004-01-01

    Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter, prospective,randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG, IgM, IgA, CD4, CD8, and CD4/CD8, and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9, among patients receiving an immune enhancing diet,IgG, IgA, CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover, among patients receiving an immune enhancing diet, when comparing preoperation to day 9 postoperation levels, increases in IgA, CD4, and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications.Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.

  18. Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

    Science.gov (United States)

    de Castro-Sobrinho, Juçara Maria; Rabelo-Santos, Silvia Helena; Fugueiredo-Alves, Rosane Ribeiro; Derchain, Sophie; Sarian, Luis Otávio Z; Pitta, Denise R; Campos, Elisabete A; Zeferino, Luiz Carlos

    2016-02-01

    Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia. © 2015 Wiley Periodicals, Inc.

  19. Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses.

    Science.gov (United States)

    Hayashi, Chie; Madrigal, Andres G; Liu, Xinyan; Ukai, Takashi; Goswami, Sulip; Gudino, Cynthia V; Gibson, Frank C; Genco, Caroline A

    2010-01-01

    Studies in humans have established that polymorphisms in genes encoding the innate immune Toll-like receptors (TLRs) are associated with inflammatory atherosclerosis. In hyperlipidemic mice, TLR2 and TLR4 have been reported to contribute to atherosclerosis progression. Human and mouse studies support a role for the oral pathogen Porphyromonas gingivalis in atherosclerosis, although the mechanisms by which this pathogen stimulates inflammatory atherosclerosis via innate immune system activation is not known. Using a genetically defined apolipoprotein E-deficient (ApoE(-/-)) mouse model we demonstrate that pathogen-mediated inflammatory atherosclerosis occurs via both TLR2-dependent and TLR2-independent mechanisms. P. gingivalis infection in mice possessing functional TLR2 induced the accumulation of macrophages as well as inflammatory mediators including CD40, IFN-gamma and the pro-inflammatory cytokines IL-1 beta, IL-6 and tumor necrosis factor-alpha in atherosclerotic lesions. The expression of these inflammatory mediators was reduced in atherosclerotic lesions from P. gingivalis-infected TLR2-deficient (TLR2(-/-)) mice. These studies provide a mechanistic link between an innate immune receptor and pathogen-accelerated atherosclerosis by a clinically and biologically relevant bacterial pathogen.

  20. Coagulation, inflammatory, and stress responses in a randomized comparison of open and laparoscopic repair of recurrent inguinal hernia

    DEFF Research Database (Denmark)

    Rahr, H B; Bendix, J; Ahlburg, P;

    2006-01-01

    with recurrent inguinal hernia were randomized to OR under local anesthesia (n = 30) or LR under general anesthesia (n = 31). The magnitude of the surgical trauma was assessed by measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial activation (von Willebrand factor), inflammation......BACKGROUND: In previous comparisons of inflammatory and stress responses to open (OR) and laparoscopic (LR) hernia repair, all operations were performed under general anesthesia. Since local anesthesia is widely used for OR, a comparison of this approach with LR seemed relevant. METHODS: Patients...... in both groups, with the CRP increase being significantly greater in the OR group. The other markers did not increase significantly. CONCLUSION: The acute phase response was more pronounced after OR, even when this was done under local anesthesia. Both techniques seemed rather atraumatic....

  1. Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders

    2016-01-01

    : To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. METHODS: We performed a PubMed literature search and retrieved...... studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis. RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease...... in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms...

  2. SiO2 and TiO2 nanoparticles synergistically trigger macrophage inflammatory responses.

    Science.gov (United States)

    Tsugita, Misato; Morimoto, Nobuyuki; Nakayama, Masafumi

    2017-04-11

    Silicon dioxide (SiO2) nanoparticles (NPs) and titanium dioxide (TiO2) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO2 and TiO2 NPs have been extensively studied, the combined toxicity of these NPs is much less understood. In this study, we observed unexpected and drastic activation of the caspase-1 inflammasome and production of IL-1β in mouse bone marrow-derived macrophages stimulated simultaneously with SiO2 and TiO2 NPs at concentrations at which these NPs individually do not cause macrophage activation. Consistent with this, marked lung inflammation was observed in mice treated intratracheally with both SiO2 and TiO2 NPs. In macrophages, SiO2 NPs localized in lysosomes and TiO2 NPs did not; while only TiO2 NPs produced ROS, suggesting that these NPs induce distinct cellular damage leading to caspase-1 inflammasome activation. Intriguingly, dynamic light scattering measurements revealed that, although individual SiO2 and TiO2 NPs immediately aggregated to be micrometer size, the mixture of these NPs formed a stable and relatively monodisperse complex with a size of ~250 nm in the presence of divalent cations. Taken together, these results suggest that SiO2 and TiO2 NPs synergistically induce macrophage inflammatory responses and subsequent lung inflammation. Thus, we propose that it is important to assess the synergistic toxicity of various combinations of nanomaterials.

  3. Epidemiology of the Systemic Inflammatory Response Syndrome (SIRS) in the emergency department.

    Science.gov (United States)

    Horeczko, Timothy; Green, Jeffrey P; Panacek, Edward A

    2014-05-01

    Consensus guidelines recommend sepsis screening for adults with systemic inflammatory response syndrome (SIRS), but the epidemiology of SIRS among adult emergency department (ED) patients is poorly understood. Recent emphasis on cost-effective, outcomes-based healthcare prompts the evaluation of the performance of large-scale efforts such as sepsis screening. We studied a nationally representative sample to clarify the epidemiology of SIRS in the ED and subsequent category of illness. This was a retrospective analysis of ED visits by adults from 2007 to 2010 in the National Hospital Ambulatory Medical Care Survey (NHAMCS). We estimated the incidence of SIRS using initial ED vital signs and a Bayesian construct to estimate white blood cell count based on test ordering. We report estimates with Bayesian modified credible intervals (mCIs). We used 103,701 raw patient encounters in NHAMCS to estimate 372,844,465 ED visits over the 4-year period. The moderate estimate of SIRS in the ED was 17.8% (95% mCI: 9.7 to 26%). This yields a national moderate estimate of approximately 16.6 million adult ED visits with SIRS per year. Adults with and without SIRS had similar demographic characteristics, but those with SIRS were more likely to be categorized as emergent in triage (17.7% versus 9.9%, pSIRS patients. Traumatic causes of SIRS comprised 10% of presentations; other traditional categories of SIRS were rare. SIRS is very common in the ED. Infectious etiologies make up only a quarter of adult SIRS cases. SIRS may be more useful if modified by clinician judgment when used as a screening test in the rapid identification and assessment of patients with the potential for sepsis. [West J Emerg Med. 2014;15(3):329-336.].

  4. Klotho suppresses the inflammatory responses and ameliorates cardiac dysfunction in aging endotoxemic mice.

    Science.gov (United States)

    Hui, Haipeng; Zhai, Yufeng; Ao, Lihua; Cleveland, Joseph C; Liu, Hongbin; Fullerton, David A; Meng, Xianzhong

    2017-02-28

    Aging augments endotoxemic cardiac dysfunction, but the mechanism remains unclear. Anti-aging protein Klotho has been found to modulate tissue inflammatory responses. We tested the hypothesis that a reduced Klotho level in aging heart plays a role in the augmented endotoxemic cardiac dysfunction. Endotoxin (0.5 mg/kg, iv) was injected to adults (4-6 months) and aging (18-20 months) C57BL/6 mice. Recombinant Klotho (10 μg/kg, iv) was administered to a group of aging mice after endotoxin injection. Cardiac function was analyzed using a microcatheter at 24 and 48 h after endotoxin administration. Myocardial levels of Klotho and heat shock protein 70 (HSP70) were determined by immunoblotting, and plasma and myocardial cytokines were analyzed using ELISA. More severe cardiac dysfunction in aging mice were accompanied by greater cytokine levels in the plasma and myocardium. Klotho was detected in the myocardial tissue. Klotho levels were lower in aging hearts and were further reduced during endotoxemia. Myocardial HSP70 levels were correlated with Klotho levels. Recombinant Klotho increased myocardial HSP70, inhibited NF-κB activation, reduced cytokine levels, and improved cardiac function in aging endotoxemic mice. Delivery of HSP70 into cultured macrophages suppressed endotoxin-induced NF-κB activation. Aging-related augmentation of inflammatory responses and cardiac dysfunction is associated with relative Klotho deficiency. Post-treatment with recombinant Klotho suppresses the inflammatory responses and improves cardiac function in aging endotoxemic mice. Klotho modulates HSP70 levels and HSP70 appears to be involved in the anti-inflammatory mechanism of Klotho. Klotho may have therapeutic potential in amelioration of aging-related endotoxemic cardiac dysfunction.

  5. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    Science.gov (United States)

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  6. Biaryl amide compounds reduce the inflammatory response in macrophages by regulating Dectin-1.

    Science.gov (United States)

    Hyung, Kyeong Eun; Lee, Mi Ji; Lee, Yun-Jung; Lee, Do Ik; Min, Hye Young; Park, So-Young; Min, Kyung Hoon; Hwang, Kwang Woo

    2016-03-01

    Macrophages are archetypal innate immune cells that play crucial roles in the recognition and phagocytosis of invading pathogens, which they identify using pattern recognition receptors (PRRs). Dectin-1 is essential for antifungal immune responses, recognizing the fungal cellular component β-glucan, and its role as a PRR has been of increasing interest. Previously, we discovered and characterized a novel biaryl amide compound, MPS 03, capable of inhibiting macrophage phagocytosis of zymosan. Therefore, in this study we aimed to identify other biaryl amide compounds with greater effectiveness than MPS 03, and elucidate their cellular mechanisms. Several MPS 03 derivatives were screened, four of which reduced zymosan phagocytosis in a similar manner to MPS 03. To establish whether such phagocytosis inhibition influenced the production of inflammatory mediators, pro-inflammatory cytokine and nitric oxide (NO) levels were measured. The production of TNF-α, IL-6, IL-12, and NO was significantly reduced in a dose-dependent manner. Moreover, the inflammation-associated MAPK signaling pathway was also affected by biaryl amide compounds. To investigate the underlying cellular mechanism, PRR expression was measured. MPS 03 and its derivatives were found to inhibit zymosan phagocytosis by decreasing Dectin-1 expression. Furthermore, when macrophages were stimulated by zymosan after pretreatment with biaryl amide compounds, downstream transcription factors such as NFAT, AP-1, and NF-κB were downregulated. In conclusion, biaryl amide compounds reduce zymosan-induced inflammatory responses by downregulating Dectin-1 expression. Therefore, such compounds could be used to inhibit Dectin-1 in immunological experiments and possibly regulate excessive inflammatory responses.

  7. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  8. Effect of mesenchymal precursor cells on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis.

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    Laura M Dooley

    Full Text Available Mesenchymal precursor cells (MPC are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model.Arthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction.Arthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls, and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs

  9. Power Doppler ultrasonographic assessment of the ankle in patients with inflammatory rheumatic diseases

    OpenAIRE

    Suzuki, Takeshi

    2014-01-01

    Ankle involvement is frequent in patients with inflammatory rheumatic diseases, but accurate evaluation by physical examination is often difficult because of the complex anatomical structures of the ankle. Over the last decade, ultrasound (US) has become a practical imaging tool for the assessment of articular and periarticular pathologies, including joint synovitis, tenosynovitis, and enthesitis in rheumatic diseases. Progress in power Doppler (PD) technology has enabled evaluation of the st...

  10. Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Silvio; Danese; Gionata; Fiorino; Erika; Angelucci; Stefania; Vetrano; Nico; Pagano; Giacomo; Rando; Antonino; Spinelli; Alberto; Malesci; Alessandro; Repici

    2010-01-01

    AIM: To investigate whether narrow band imaging (NBI) is a useful tool for the in vivo detection of angiogenesis in inflammatory bowel disease (IBD) patients. METHODS: Conventional and NBI colonoscopy was performed in 14 patients with colonic inflammation (8 ulcerative colitis and 6 Crohn’s disease). Biopsy samples were taken and CD31 expression was assayed immuno- histochemically; microvascular density was assessed by vessel count. RESULTS: In areas that were endoscopically normal but positive on NBI, ther...

  11. The Inflammatory-Nutritional Index: assessing nutritional status and prognosis in gastrointestinal and lung cancer patients

    OpenAIRE

    Carla Alberici Pastore; Silvana Paiva Orlandi; Maria Cristina Gonzalez

    2014-01-01

    Objective: To evaluate the prognostic capacity of the Inflammatory-Nutritional Index (INI) in gastrointestinal and lung cancer patients. Methods: Longitudinal study, including patients from a chemotherapy service in Brazil, between July 2008 and May 2010. INI (Albumin/CRP) and nutritional status (by Subjective Global Assessment - SGA) were evaluated. Risk INI was defined as lower than 0.35. The mean follow-up of survival was 1.6 year. Statistical analyses were performed using Stata 11.1™. Res...

  12. A role for PFKFB3/iPFK2 in metformin suppression of adipocyte inflammatory responses.

    Science.gov (United States)

    Qi, Ting; Chen, Yanming; Li, Honggui; Pei, Ya; Woo, Shih-Lung; Guo, Xin; Zhao, Jiajia; Qian, Xiaoxian; Awika, Joseph; Huo, Yuqing; Wu, Chaodong

    2017-07-01

    Metformin improves obesity-associated metabolic dysregulation, but has controversial effects on adipose tissue inflammation. The objective of the study is to examine the direct effect of metformin on adipocyte inflammatory responses and elucidate the underlying mechanisms. Adipocytes were differentiated from 3T3-L1 cells and treated with metformin at various doses and for different time periods. The treated cells were examined for the proinflammatory responses, as well as the phosphorylation states of AMPK and the expression of PFKFB3/iPFK2. In addition, PFKFB3/iPFK2-knockdown adipocytes were treated with metformin and examined for changes in the proinflammatory responses. The following results were obtained from the study. Treatment of adipocytes with metformin decreased the effects of lipopolysaccharide on inducing the phosphorylation states of JNK p46 and on increasing the mRNA levels of IL-1β and TNFα. In addition, treatment with metformin increased the expression of PFKFB3/iPFK2, but failed to significantly alter the phosphorylation states of AMPK. In PFKFB3/iPFK2-knockdown adipocytes, treatment with metformin did not suppress the proinflammatory responses as did it in control adipocytes. In conclusion, metformin has a direct effect on suppressing adipocyte proinflammatory responses in an AMPK-independent manner. Also, metformin increases adipocyte expression of PFKFB3/iPFK2, which is involved in the anti-inflammatory effect of metformin. © 2017 Society for Endocrinology.

  13. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

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    Felix W Santiago

    Full Text Available Mayaro virus (MAYV, an alphavirus similar to chikungunya virus (CHIKV, causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

  14. Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response.

    Science.gov (United States)

    Santiago, Felix W; Halsey, Eric S; Siles, Crystyan; Vilcarromero, Stalin; Guevara, Carolina; Silvas, Jesus A; Ramal, Cesar; Ampuero, Julia S; Aguilar, Patricia V

    2015-01-01

    Mayaro virus (MAYV), an alphavirus similar to chikungunya virus (CHIKV), causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals. Currently, the immune response and its role in the development of MAYV-induced persistent arthralgia remain unknown. In this study, we evaluated the immune response of individuals with confirmed MAYV infection in a one-year longitudinal study carried out in Loreto, Peru. We report that MAYV infection elicits robust immune responses that result in the development of a strong neutralizing antibody response and the secretion of pro-inflammatory immune mediators. The composition of these inflammatory mediators, in some cases, differed to those previously observed for CHIKV. Key mediators such as IL-13, IL-7 and VEGF were strongly induced following MAYV infection and were significantly increased in subjects that eventually developed persistent arthralgia. Although a strong neutralizing antibody response was observed in all subjects, it was not sufficient to prevent the long-term outcomes of MAYV infection. This study provides initial immunologic insight that may eventually contribute to prognostic tools and therapeutic treatments against this emerging pathogen.

  15. Anti-inflammatory activities of isorhamnetin-3-O-galactoside against HMGB1-induced inflammatory responses in both HUVECs and CLP-induced septic mice.

    Science.gov (United States)

    Kim, Tae Hoon; Ku, Sae-Kwang; Bae, Jong-Sup

    2013-02-01

    High mobility group box 1 (HMGB1) protein is a crucial nuclear cytokine that elicits severe vascular inflammatory diseases. Oenanthe javanica (water dropwort) extract has anti-arrhythmic, neuroprotective and anti-diabetic activity. However, isorhamnetin-3-O-galactoside (I3G), an active compound from O. javanica, is not researched well for its biological activity. Here, we investigated the anti-inflammatory activities of I3G by monitoring the effects of I3G on the lipopolysaccharide (LPS) or cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1 or CLP-mediated modulation of inflammatory responses. I3G potently inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. I3G also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. Further studies revealed that I3G suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by HMGB1. In addition, I3G reduced CLP-induced HMGB1 release and sepsis-related mortality. Given these results, I3G should be viewed as a candidate therapeutic agent for the treatment of severe vascular inflammatory diseases such as sepsis or septic shock via inhibition of the HMGB1 signaling pathway.

  16. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

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    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  17. Muscle cells challenged with saturated fatty acids mount an autonomous inflammatory response that activates macrophages

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    Pillon Nicolas J

    2012-10-01

    Full Text Available Abstract Obesity is associated with chronic low-grade inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of cytokines which in turn impact on the surrounding tissue. However, inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary glucose and a major determinant of glycemia, the origin and consequence of muscle inflammation in the development of insulin resistance are poorly understood. We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and unsaturated fatty acids. Inflammatory pathway activation and cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc exposed to 0.2 mM palmitate or palmitoleate. Conditioned media thereof, free of fatty acids, were then tested for their ability to activate RAW264.7 macrophages. Palmitate -but not palmitoleate- induced IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway. Palmitate (0.2 mM alone did not induce insulin resistance in muscle cells, yet conditioned media from palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype. These results demonstrate that low concentrations of palmitate activate autonomous inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to insulin resistance in vivo.

  18. Suppression of adipogenesis by pathogenic seipin mutant is associated with inflammatory response.

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    Wenjie Qiu

    Full Text Available BACKGROUND: While pathogenic mutations in BSCL2/Seipin cause congenital generalized lipodystrophy, the underlying mechanism is largely unknown. In this study, we investigated whether and how the pathogenic missense A212P mutation of Seipin (Seipin-A212P inhibits adipogenesis. METHODOLOGY/RESULTS: We analyzed gene expression and lipid accumulation in stable 3T3-L1 cell lines expressing wild type (3T3-WT, non-lipodystrophic mutants N88S (3T3-N88S and S90L (3T3-S90L, or lipodystrophic mutant A212P Seipin (3T3-A212P. When treated with adipogenic cocktail, 3T3-WT, 3T3-N88S and 3T3-S90L cells exhibited proper differentiation into mature adipocytes, indistinguishable from control 3T3-L1 cells. In contrast, adipogenesis was significantly impaired in 3T3-A212P cells. The defective adipogenesis in 3T3-A212P cells could be partially rescued by either PPARγ agonist or PPARγ overexpression. Gene expression profiling by microarray revealed that inhibition of adipogenesis was associated with activation of inflammatory genes including IL-6 and iNOS. We further demonstrated that Seipin-A212P expression at pre-differentiation stages significantly activated inflammatory responses by using an inducible expression system. The inflammation-associated inhibition of adipogenesis could be rescued by treatment with anti-inflammatory agents. CONCLUSIONS: These results suggest that pathogenic Seipin-A212P inhibits adipogenesis and the inhibition is associated with activation of inflammatory pathways at pre-differentiation stages. Use of anti-inflammatory drugs may be a potential strategy for the treatment of lipodystrophy.

  19. /sup 111/In autologous leucocytes in the diagnosis and assessment of inflammatory bowel disease. [Tropolone

    Energy Technology Data Exchange (ETDEWEB)

    Saverymuttu, S.H.; Peters, A.M.; Chadwick, V.S.; Hodgson, H.J.; Lavender, J.P. (Hammersmith Hospital, London (UK))

    1982-01-01

    Indium-111 autologous leukocyte scanning is now established as an effective method of localising sepsis (Ascher and others, 1980). In view of the extensive leucocyte infiltration of the intestinal wall in inflammatory bowel disease, the authors have prospectively studied the use of indium-111 labelled white cells in a variety of inflammatory bowel disorders. Leukocytes were labelled in 68 patients using /sup 111/In acetylacetonate and in 18 patients /sup 111/In tropolone. Crude mixed leukocytes preparations were used in 74 patients and pure neutrophil preparation used in 12 patients. Gamma scans over the abdomen were performed from 40 min later after re-injection of the labelled cells and assessed. /sup 111/In-tropolone labelling appeared to offer the advantage over /sup 111/In-acac labelling in localising inflamed bowel earlier. The technique of /sup 111/In-leukocyte scanning offers several advantages over the alternative technique of imaging diseased bowel using gallium-67 citrate. Indium-111 leukocyte scanning provides a novel approach to the problem of diagnosis and assessment of inflammatory bowel disease. It is non-invasive, requires no bowel preparation and this is safe in the acutely sick patient where conventional radiological imaging methods may be hazardous. /sup 111/In faecal excretion provides an objective assessment of disease activity which should prove useful in evaluating treatment regimes.

  20. 11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes.

    Science.gov (United States)

    Itoi, Saori; Terao, Mika; Murota, Hiroyuki; Katayama, Ichiro

    2013-10-18

    The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactive cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10(-13) M cortisol, whereas 1 × 10(-5) M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol concentrations by 11β-HSD1 appears to modulate expression of inflammatory cytokines in NHEKs. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules.

    Science.gov (United States)

    Paredes-Juarez, Genaro A; de Haan, Bart J; Faas, Marijke M; de Vos, Paul

    2013-12-28

    Alginate-based microcapsules are used for immunoisolation of cells to release therapeutics on a minute-to-minute basis. Unfortunately, alginate-based microcapsules are suffering from varying degrees of success, which is usually attributed to differences in tissue responses. This results in failure of the therapeutic cells. In the present study we show that commercial, crude alginates may contain pathogen-associated molecular patterns (PAMPs), which are recognized by the sensors of the innate immune system. Known sensors are Toll-like receptors (TLRs), NOD receptors, and C-type lectins. By using cell-lines with a non-functional adaptor molecule essential in Toll-like receptor signaling, i.e. MyD88, we were able to show that alginates signal mainly via MyD88. This was found for low-G, intermediate-G, and high-G alginates applied in calcium-beads, barium-beads as well as in alginate-PLL-alginate capsules. These alginates did stimulate TLRs 2, 5, 8, and 9 but not TLR4 (LPS receptor). Upon implantation in rats these alginates provoked a strong inflammatory response resulting in fibrosis of the capsules. Analysis demonstrated that commercial alginates contain the PAMPs peptidoglycan, lipoteichoic acid, and flagellin. By applying purification procedures, these PAMPs were largely removed. This was associated with deletion of the inflammatory tissue responses as confirmed by an implantation experiment in rats. Our data also show that alginate itself does not provoke TLR mediated responses. We were able to unravel the sensor mechanism by which contaminants in alginates may provoke inflammatory responses.

  2. HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

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    Mudan Lu

    2015-01-01

    Full Text Available Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE; however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

  3. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Felix Kaspar

    2016-01-01

    Full Text Available Objective. This study compared acute and late effect of single-bout endurance training (ET and high-intensity interval training (HIIT on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL, IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1, insulin growth factor 1 (IGF-1, and C-reactive protein (CRP. Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p=0.047 and a decrease of MCP-1 (−17.9%; p=0.03. Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  4. Lipid Bodies: Inflammatory Organelles Implicated in Host-Trypanosoma cruzi Interplay during Innate Immune Responses

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    Heloisa D'Avila

    2012-01-01

    Full Text Available The flagellated protozoa Trypanosoma cruzi is the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. Acute Chagas' disease elicits a strong inflammatory response. In order to control the parasite multiplication, cells of the monocytic lineage are highly mobilized. Monocyte differentiation leads to the formation of phagocytosing macrophages, which are strongly activated and direct host defense. A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets. These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators. This review covers current knowledge on lipid bodies elicited by the acute Chagas' disease within inflammatory macrophages and discusses the role of these organelles in inflammation. The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

  5. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

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    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  6. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...... Germany (600 mg) × 3/day/1 week) group (n = 13) in a double-blinded-fashion. Tendon biopsies were taken from the painful and a healthy region of the same tendon 2 h after 1 h running. Gene-expression of several targets was analysed in the sampled Achilles tendon biopsies. The mRNA for TGF-ß, collagen...

  7. [Inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide-stimulated human mast cells].

    Science.gov (United States)

    Zhou, Yun-jiang; Wang, Hu; Li, Li; Sui, He-huan; Huang, Jia-jun

    2015-06-01

    This study is to investigate the inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide(LPS)-stimulated HMC-1 mast cells. The cytotoxicity of kaempferol to HMC-1 mast cells were analyzed by using MTT assay and then the administration concentrations of kaempferol were established. Histamine, IL-6, IL-8, IL-1β and TNF-α were measured using ELISA assay in activated HMC-1 mast cells after incubation with various concentrations of kaempferol (10, 20 and 40 µmol.L-1). Western blot was used to test the protein expression of p-IKKβ, IκBα, p-IκBα and nucleus NF-κB of LPS-induced HMC-1 mast cells after incubation with different concentrations of kaempferol. The optimal concentrations of kaempferol were defined as the range from 5 µmol.L-1 to 40 µmol.L-1. Kaempferol significantly decreased the release of histamine, IL-6, IL-8, IL-1β and TNF-α of activated HMC-1 mast cells (Pkaempferol, the protein expression of p-IKKβ, p-IKBa and nucleus NF-κB (p65) markedly reduced in LPS-stimulated HMC-1 mast cells (Pkaempferol markedly inhibit mast cell-mediated inflammatory response. At the same time, kaempferol can inhibit the activation of IKKβ, block the phosphorylation of IκBα, prevent NF-KB entering into the nucleus, and then decrease the release of inflammatory mediators.

  8. A single administration of fish oil inhibits the acute inflammatory response in rats.

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    de Arruda, Laura Lícia Milani; Ames, Franciele Queiroz; de Morais, Damila Rodrigues; Grespan, Renata; Gil, Ana Paula Maziero; Silva, Maria Angélica Raffaini Covas Pereira; Visentainer, Jesuí Vergílio; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2017-08-01

    To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response. The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay. FOP treatment (30 and 300 mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300 mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300 mg/kg) reduced NO, TNF-α, IL-1β, and IL-6 concentrations in the pleural exudate. The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

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

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    Kishore V L Parsa

    2006-07-01

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

  10. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.

    Science.gov (United States)

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-12-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.

  11. Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses.

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    Beryl Wen

    Full Text Available Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416 expression and promoted