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The aim of the present study was to investigate the relationship between the levels of pro-inflammatory [interleukin 6 (IL-6), IL-8, tumour necrosis factor alpha (TNF-α)], anti-inflammatory cytokines [IL-10, soluble TNF receptor type I (TNFsrI), TNFsrII], and the production of nitric oxide (NO) during a 1-week period in 23 patients with severe sepsis. The highest levels of pro-inflammatory cytokines...
The deleterious effects of interleukin 1 (IL-1) on insulin-producing β-cells are partly mediated by the generation of the free radical nitric oxide (NO). We aimed to assess the effect of several steroidal hormones on IL-1β-induced inhibition of rat islet insulin secretion in vitro, and their possible regulatory effects on NO production. Incubation of newborn rat islets for 24 h in the presence of...
We have examined the effects of various antioxidants and inhibitors of redox-sensitive signal transduction pathways on induction of interleukin 8 (IL-8) gene by NO in monocytic U937 cells. We have observed that nitrosoglutathione or another NO-generating compound spermine NONOate caused significant accumulation of IL-8 mRNA. Pretreatment of cells with pyrrolidine dithiocarbamate or with antioxidants,...
Regulation of uncoupling protein-2 (UCP-2) in β-cells is presently unclear but may involve oxidative stress. We tested for regulation by β-cell toxic cytokines. Exposure to interleukin-1β (IL-1β, 10 ng/ml) for 6 h down-regulated UCP-2 mRNA in clonal INS-1 cells, by 37 +/- 7%, and in rat pancreatic islets, by 55 +/- 8%. In contrast, a 6 h exposure to IL-1β did not affect viability as assessed by the...
The stress-activated protein kinase c-Jun NH 2 -terminal kinase (JNK) is a central signal for interleukin-1β (IL-1β)-induced apoptosis in insulin-producing β-cells. The cell-permeable peptide inhibitor of JNK (JNKI1), that introduces the JNK binding domain (JBD) of the scaffold protein islet-brain 1 (IB1) inside cells, effectively prevents β-cell death caused by this cytokine. To define the...
The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the developing lung. Our goals were to evaluate the effect of antioxidants (AO) on apoptosis and release of cytokines in freshly isolated FTIIP (day-19) in the presence of 95% O 2 and/or nitric oxide (NO). There...
We investigated the effects of the Th 2 -like cytokines IL-4 and IL-13 and of IL-10 on the induction of iNOS and NO production in rat eosinophils. Addition of mIL-4 to the eosinophil culture increased iNOS activity and nitrite production but did not improve the stimulatory effect of IFN-γ and LPS. In contrast to eosinophils, addition of mIL-4 to macrophage cultures inhibited the iNOS expression...
Interleukin-6 (IL-6) reduces myocardial haemodynamics. However, the intrinsic mechanisms of IL-6 effects are not known. We hypothesized that nitric oxide (NO) synthesised by neuronal synthase (nNOS) can be the molecular mediator of IL-6-mediated cardiac effects. Thus, we investigated in vivo after IL-6 acute administration: (1) the role of NO pathway; (2) the importance of NO derived from nNOS located...
Pro-inflammatory factors such as the adipokine leptin and cytokine tumor necrosis factor-α (TNFα) have been implicated in the onset of myocardial dysfunction in ischemia–reperfusion injury, sepsis, heart failure, viral myocarditis and cardiac allograft rejection. Although circulating TNFα and leptin levels are both elevated under a variety of inflammatory conditions, it remains unknown whether TNFα...
The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 β (IL-1β). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague–Dawley rats receiving during 60min ICV infusion of: 0.9% NaCl (5μl/h; series 1), IL-1β (100ng/h;...
Objective. To compare in cell culture endothelin-1 (ET-1) production, receptor density, and effect on macromolecular synthesis by articular chondrocytes (AC). Methods. AC were isolated from 1-month and 18-month old rats and cultured as monolayers. They were incubated with ET-1 without or with iNOS inhibitors, nitro-l-arginine methyl ester (l-NAME) or guanylate cyclase inhibitor, LY83583 and then [...
Interleukin-8 (IL-8), a member of the CXC chemokine family, plays an important role in the modulation of multiple biological functions in endothelial cells containing the receptors CXCR1 and CXCR2. It has previously been shown that IL-8 directly enhances endothelial cell survival, and stimulates the production of matrix metalloproteinases, which in turn regulates angiogenesis. However, its role in...
Advanced glycation endproducts (AGEs) accumulate on long-lived protein deposits, e.g. those composed of β 2 -microglobulin (in dialysis-related amyloidosis) or β-amyloid peptide (in Alzheimer’s disease). When AGEs bind to the “receptor for advanced glycation endproducts”, they activate redox-sensitive transcription factors such as NF-κB, and subsequently induce the expression of pro-inflammatory...
The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both physiological and pathological functions. The present study examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of iNOS and proinflammatory cytokine production in RAW 264.7 cells in response to Salmonella enterica serovar Typhimurium porins. By use of Western blotting for iNOS detection...
Lipopolysaccharide (LPS) has been known to produce inflammatory modulators such as tumor necrosis factor α (TNF-α) or nitric oxide (NO). In this study, we examined the effects of nicotine on LPS enhanced NO synthesis and inducible nitric oxide synthase (iNOS) expression in macrophages. LPS-induced NO synthesis and iNOS expression were significantly decreased by nicotine. To investigate the signaling...
In this study the effects of nitric oxide (NO) on intimal hyperplasia (IH) were evaluated in an ex-vivo model of human saphenous vein (SV).SV segments were cultured in conditions able to reproduce IH (FCS), or in medium alone (RPMI), or in presence of a NO donor (NO). Osteopontin (OPN) and Interleukin (IL)-6 were determined in the medium at different culture times and in the tissue, at the end of...
Previously, we have shown that electroacupuncture (EA) in rats decreased eosinophil infiltration into the pulmonary tissue (PT) and in the bronchoalveolar lavage (BAL) in an experimental model of asthma. Th2 cytokines, leukotriene B4 (LTB4) and nitric oxide (NO) are involved in the asthma inflammatory process. The aim of this study was to verify the effects of EA on these asthma mediators. Male Wistar...
Macrophages are the target cells for mycobacterial infections. They are also largely responsible for intracellular killing of mycobacteria, which is dependent on the cytokine environment. Interferon-γ (IFN-γ) is chiefly responsible for macrophage activation and bactericidal capacity while Th2 cytokines have a contrasting effect. However, cytokines rarely act in isolation during an infection. Instead,...
Early apoptotic neutrophils but not secondary necrotic ones down-regulate LPS-induced proinflammatory cytokine production of macrophages, thereby contributing to the resolution of inflammation. IFN-γ is also a well-known stimulant of macrophages, but how the apoptotic neutrophils affect IFN-γ-stimulated macrophages remains largely unexplored. Since IFN-γ induces the expression of inducible nitric...
Regulation of macrophage activity by T H 1/2 cytokines is important to maintain the balance of immunity to provide adequate protective immunity while avoiding excessive inflammation. IFN-γ and IL-4 are the hallmark T H 1 and T H 2 cytokines, respectively. In avian species, information concerning regulation of macrophage activity by T H 1/2 cytokines is limited. Here,...
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