Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of inducible nitric oxide synthase (iNOS) on ischemic myocardial damage and angiogenic process in genetically deficient iNOS (iNOS(-/-)) mice and wild-type littermates (iNOS(+/+)), with and without streptozotocin-induced (70 mg/kg intravenously) diabetes. After ischemia (25 min) and reperfusion (120 min), both iNOS(+/+) and iNOS(-/-) diabetic mice (blood glucose 22 mmol/l) had myocardial infarct size greater than their respective nondiabetic littermates (P < 0.01). Myocardial infarct size (P < 0.05), apoptotic index (P < 0.005), and tissue levels of tumor necrosis factor (P < 0.01), interleukin-6 (P < 0.01), and interleukin-18 (P < 0.01) were higher in nondiabetic iNOS(-/-) mice compared with nondiabetic iNOS(+/+) mice. As compared with diabetic iNOS(-/-) mice, diabetic iNOS(+/+) mice showed a greater infarct size (P < 0.01) associated with the highest tissue levels of nitrotyrosine and proinflammatory cytokines, as well as apoptosis. The beneficial role of iNOS in modulating defensive responses against ischemia/reperfusion injury seems to be abolished in diabetic mice.
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PMID:Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice. 1474 98

Erectile and endothelial dysfunction may have some shared pathways through a defect in nitric oxide activity. We evaluated associations between erectile function, endothelial function and markers of systemic vascular inflammation in 80 obese men, aged 35-55 yr, divided into two equal groups according to the presence/absence of erectile dysfunction. Compared with non-obese age-matched men [no.=50, body mass index (BMI)=24 +/- 1], obese men (all) had impaired indices of endothelial function as suggested by the reduced mean blood pressure and platelet aggregation responses to L-arginine, and higher circulating concentrations of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), as well as C-reactive protein (CRP). The mean erectile function score was 14 +/- 4 (range 7-19) in obese men with erectile dysfunction and 23.5 +/- 1 (range 22-25) in obese men without erectile dysfunction. Endothelial function showed a greater impairment in impotent obese men as compared with potent obese men. The mean blood pressure and platelet aggregation decreases following L-arginine were -1.5 +/- 1.1 mmHg and -1.1 +/- 1.2%, respectively, in obese men with erectile dysfunction, and -3.4 +/- 1.2 mmHg and -5.6 +/- 2.1%, respectively, in obese men without erectile dysfunction (p < 0.01). Circulating CRP levels were significantly higher in obese men with erectile dysfunction as compared with obese men without erectile dysfunction (p < 0.05). Erectile function score was positively associated with mean blood pressure responses to L-arginine and negatively associated with BMI, waist-to-hip ratio (WHR), and CRR Erectile and endothelial dysfunction associate in obese men and may contribute to their raised cardiovascular risk through impaired nitric oxide availability elicited by a low-grade inflammatory state.
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PMID:Erectile dysfunction associates with endothelial dysfunction and raised proinflammatory cytokine levels in obese men. 1550 91

We report the program of gene expression during osteoclast formation from RAW264.7 cell precursors in response to RANK-ligand (RANK-L) using a combination of quantitative real time PCR and Affymetrix gene chip assays. We found that genes obligatory to osteoclast formation and function, namely tartrate-resistant acid phosphatase, cathepsin K, beta3 integrin, and calcitonin receptors, were up-regulated by RANK-L markedly by up to approximately 2000-fold. In contrast, we found a cluster of genes that were significantly down-regulated: these included interleukin-18, insulin-like growth factor-1, interleukin-6 receptor, and cathepsins B, C, and L. These results from real time PCR were broadly concordant with those obtained from Affymetrix. We also explored the expression of the transcription factors of the NFAT and NFkappaB family at days 3 and 5 of culture. Whereas NFATc1 expression was increased significantly at days 3 and 5 following RANK-L exposure, there were no significant increases in the expression of NFkappaB subunits, namely p65, p50, c-Rel, IkappaBalpha, and IkappaBbeta. There were also no significant differences in transcription modulator expression between days 3 and 5, except for c-Rel and NFATc4, which were both decreased significantly at day 5. The studies suggest RANK-L regulates the expression only of NFATc1, while it signals through both NFATc1 and NFkappaB.
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PMID:RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during osteoclast formation. 1556 62

Several lines of evidence indicate that increased inflammatory activity in peripheral blood is associated with the acute coronary syndrome. Systemic inflammation in clinically stable conditions of coronary artery disease has been less studied. We examined cytokine profiles in 20 patients who had acute coronary syndrome, 45 who had angiographically verified coronary artery disease and stable angina pectoris, and 45 healthy controls. Circulating levels of C-reactive protein, interleukin-1 receptor antagonist, interleukin-2 receptor, interleukin-6, interleukin-10, and interleukin-18 were determined. Subpopulations of peripheral immune cells, including neutrophil-platelet aggregates, were analyzed by 3-color flow cytometry using a panel of monoclonal antibodies. Patients who had acute coronary syndrome and stable angina pectoris had significantly higher levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist than did controls, whereas levels of interleukin-2 receptor, interleukin-10, and interleukin-18 were similar across groups. Patients had significantly more neutrophils, and the numbers of neutrophil-platelet aggregates were particularly large in patients who had stable angina pectoris. High levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist in patients were significantly related to numbers of neutrophils and neutrophil-platelet aggregates but not to other immune cell subpopulations. The data suggest that the interaction between neutrophils and platelets is an important component of proinflammatory activity seen in peripheral blood of stable and unstable forms of coronary artery disease.
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PMID:Circulating levels of proinflammatory cytokines and neutrophil-platelet aggregates in patients with coronary artery disease. 1569 27

Neural progenitor cells (NPCs) in developing and adult CNS are capable of giving rise to various neuronal and glial cell populations. Neurogenesis in the adult hippocampus has been found to be inhibited by a proinflammatory cytokine, interleukin-6 (IL-6), suggesting that activated microglia in the inflamed brain may control neurogenesis. Yet, little is known about the effect of microglia-derived factors on the cell fate of embryonic NPCs. In this study, we show that neurons with betaIII-tubulin immunoreactivity in the NPC culture were reduced by the condition media collected from microglia treated with endotoxin lipopolysaccharide (LPS/M-CM). Treatment with pentoxifylline (PTX), an inhibitor for tumor necrosis factor-alpha (TNF-alpha) secretion from LPS-activated microglia, blocked the reduction of betaIII-tubulin+ cells in NPC culture. Furthermore, treatment of NPCs with interleukin-18 (IL-18), a recently discovered proinflammatory cytokine, also decreased the number of betaIII-tubulin+ cells in a dose- and time-dependent manner. Surprisingly, we also observed that the remaining betaIII-tubulin+ cells in the LPS/M-CM-treated culture exhibited more branching neurites. Thus, the activated microglia-derived cytokines, TNF-alpha and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture.
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PMID:Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. 1605 98

Mycoplasma pneumoniae sometimes causes central nervous system manifestations, which may involve the host immune response, as the organism does not directly damage neural cells, or release toxins. Therefore we measured the levels of interleukin-6, interleukin-8, interleukin-18, interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta1 in serum and cerebrospinal fluid samples from patients who manifested central nervous system manifestations during acute M. pneumoniae infection. The subjects were nine patients with early-onset encephalitis (central nervous system disease onset within 7 days from the onset of fever), four with late-onset encephalitis (onset at 8 days or later), three with encephalitis but without fever, and three with aseptic meningitis. Intrathecal elevations of interleukin-6 and interleukin-8 in all four types of central nervous system manifestations, and of interleukin-18 in late-onset encephalitis were observed. None of the cerebrospinal fluid samples contained detectable levels of interferon-gamma, tumor necrosis factor-alpha, or transforming growth factor-beta1. In conclusion, interleukin-6, interleukin-8, and interleukin-18 might be involved in the inflammatory process leading to the central nervous system manifestations caused by M. pneumoniae.
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PMID:Cytokines involved in CNS manifestations caused by Mycoplasma pneumoniae. 1608 54

Inflammation in the central nervous system is an early hallmark of many neurodegenerative diseases including Alzheimer's disease (AD). Recently, increasing evidence suggests that hypercholesterolemia during midlife and abnormalities in the cholesterol metabolism could have an important role in the pathogenesis of AD. In the present study, we have evaluated the effect of high cholesterol (HC) diet on the expression of interleukin-6 (IL-6), a cytokine involved in neurodegeneration, and caspase-1, that is responsible for the cleavage of the precursors of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18) in the brain of apolipoprotein E (Apo E) knock-out (KO) and wild type (WT) mice. The density of IL-6-positive cells was increased in the hippocampus (p<0.0001) and the dorsal part of the cortex (p<0.001) of KO and WT mice on HC diet (KOHC and WTHC mice, respectively) compared to KO and WT mice on ND (KOND and WTND mice, respectively). KOHC mice had increased caspase-1 positive cells and staining intensity in the hippocampus in comparison with WTHC mice (p<0.01). In the hippocampus, the density of caspase-1 positive cells was also higher in KOHC compared to KOND mice (p<0.05) and KOHC compared with WTHC mice (p<0.01). There was a major increase in caspase-1 immunoreactivity and cell density in both the dosal part of the cortex (p<0.001) and the lateral part of the cortex (p<0.005) in KO and WT mice on HC diet compared to ND. The findings of the present study indicate that chronic exposure to HC diet increases the expression of the two important inflammatory mediators IL-6 and caspase-1 in the brain of KO and WT mice. In the case of caspase-1, we report a major difference in the effect of HC diet on the KO mice compared to WT mice in the hippocampus. Increased expression of inflammatory mediators involved in neurodegeneration could be a potential mechanism by which hypercholesterolemia and HC diet increase the risk of AD.
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PMID:High cholesterol diet results in increased expression of interleukin-6 and caspase-1 in the brain of apolipoprotein E knockout and wild type mice. 1619 27

Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.
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PMID:Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice. 1716 28

The present study investigated the possibility that acute stress might activate microglial cells. Wistar rats were exposed to 2 h period of restraint combined with water immersion stress prior to brain analysis by immunohistochemistry with OX-42, a marker of complement receptor CR3. A single session of stress provoked robust morphological microglial activation in the thalamus, hypothalamus, hippocampus, substantia nigra and central gray. These effects appeared as early as at 1 h of exposure and were further intensified at 2 h. Morphological activation was not accompanied with changes in markers of functional activation or of inflammation including interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS). Similar results were obtained with mice where the effects of stress were compared in animals null for interleukin-18 (IL-18 KO), a cytokine previously demonstrated to be modulated by stress and to contribute to microglia activation. The results demonstrated significant reduction of stress-induced microglial activation in IL-18 KO mice. The present study reports evidence that physical/emotional stress may induce morphological microglial activation in the brain and this activation is in part mediated by interleukin-18.
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PMID:Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. 1743 55

The offspring of type 2 diabetic patients are at elevated risk for type 2 diabetes and cardiovascular disease. The aim of our study was to characterize the role of various biomarkers of endothelial activation in a cohort of offspring of type 2 diabetic subjects and to assess the association of adhesion molecules with inflammatory markers and metabolic parameters. Cytokine and adhesion molecule levels were measured in 19 healthy subjects and in 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance and 20 with impaired glucose tolerance). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. The levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-Selectin and vascular adhesion protein-1 were not increased in offspring of type 2 diabetic subjects, but they correlated with inflammatory markers (C-reactive protein, tumor necrosis-alpha, interleukin-6, interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-8, interleukin-10 and interleukin-18). In conclusion, the levels of adhesion molecules were not elevated in the prediabetic state. Inflammatory markers and adhesion molecules were correlated suggesting that low-grade inflammation may precede the elevation of levels of adhesion molecules.
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PMID:Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects. 1756 May 80


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