UNIPROT:P10145 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
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PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.
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PMID:Intrathecal release of pro- and anti-inflammatory cytokines during stroke. 940 56

Chemokines constitute a constantly growing family of small inflammatory cytokines. They have been implied in many different diseases of the CNS including trauma, stroke and inflammation, e.g., multiple sclerosis. In this review we focus on the role of chemokines in infectious meningitis of bacterial or viral origin. In experimental bacterial meningitis induced by Listeria monocytogeneses both CXC and CC chemokines namely MIP-1alpha, MIP-1beta and MIP-2 are produced intrathecally by meningeal macrophages and leukocytes which infiltrate into the CNS. In patients with bacterial meningitis, IL-8, GROalpha, MCP-1, MIP-1alpha and MIP-1beta are detectable in the CSF. These chemokines contribute to CSF mediated chemotaxis on neutrophils and PBMC in vitro. In viral meningitis IL-8, IP-10 and MCP-1 are identified in the CSF to be responsible for chemotactic activity on neutrophils, PBMC and activated T cells. Taken collectively these data indicate that the recruitment of leukocytes in infectious meningitis involves the intrathecal production of chemokines.
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PMID:Chemokines and chemotaxis of leukocytes in infectious meningitis. 962 95

We have previously demonstrated that endothelin-1 (Et-1) induces human central nervous system-derived endothelial cells (CNS-EC) to produce and secrete the chemokine interleukin 8 (IL-8). In the present study, we use specific inhibitors and activators to elucidate the signal transduction pathways involved in this process. Et-1-induced IL-8 production was blocked by ET(A) receptor antagonist BQ610, but not by ET(B) receptor antagonist BQ788, demonstrating that CNS-EC activation is initiated by Et-1 binding to the ET(A) receptor. IL-8 mRNA expression is blocked by the protein kinase C inhibitor bisindolylmaleimide or protein tyrosine kinase inhibitors, genestein and geldanamycin, establishing the involvement of the protein kinase C and protein tyrosine kinase pathways in the activation process. The transcription factor, NF-kappaB, is involved in Et-1 activation as determined by specific inhibitors of translocation and direct analysis of DNA-binding proteins. Neither inhibition nor activation of cAMP-dependent protein kinase affected IL-8 production in the absence or presence of Et-1. Similarly, no effect was observed upon inhibition of protein phosphatases by okadaic acid. Thus, the signal transduction process induced by Et-1 in CNS-EC, leading to increased mRNA IL-8 expression, is initiated by Et-1 binding to ET(A) receptor followed by subsequent activation of protein kinase C, protein tyrosine kinase, and NF-kappaB. Because increased expression of Et-1 is associated with hypertension and stroke and IL-8 is likely to be involved in the accumulation of neutrophils causing tissue damage in ischemic/reperfusion injury, identification of the mechanism involved in the Et-1-induced increase in IL-8 production may have significant therapeutic value.
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PMID:Endothelin-1-induced interleukin-8 production in human brain-derived endothelial cells is mediated by the protein kinase C and protein tyrosine kinase pathways. 1043 17

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.
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PMID:Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds. 1048 94

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.
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PMID:Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke. 1170 Nov 51

Enriched populations of human microglial cells were isolated from mixed cell cultures prepared from embryonic human telencephalon tissues. Human microglial cells exhibited cell type-specific antigens for macrophage-microglia lineage cells including CD11b (Mac-1), CD68, B7-2 (CD86), HLA-ABC, HLA-DR and ricinus communis aggulutinin lectin-1 (RCA-1), and actively phagocytosed latex beads. Gene expression and protein production of cytokines, chemokines and cytokine/chemokine receptors were investigated in the purified populations of human microglia. Normal unstimulated human microglia expressed constitutively mRNA transcripts for interleukin- 1beta (IL-1beta) -6, -8, -10, -12, -15, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and monocyte chemoattractant protein-1 (MCP-1), while treatment with lipopolysaccharide (LPS) or amyloid beta peptides (Abeta) led to increased expression of mRNA levels of IL-8, IL-10, IL-12, TNF-alpha, MIP-1alpha, MIP-1beta, and MCP-1. Human microglia, in addition, expressed mRNA transcripts for IL-1RI, IL-1RII, IL-5R, IL-6R, IL-8R, IL-9R, IL-10R, IL-12R, IL-13R, and IL-15R. Enzyme-linked immunosorbent assays (ELISA) showed increased protein levels in culture media of IL-1beta, IL-8, TNF-alpha, and MIP-1alpha in human microglia following treatment with LPS or Abeta. Increased TNF-alpha release from human microglia following LPS treatment was completely inhibited with IL-10 pretreatment, but not with IL-6, IL-9, IL-12, IL-13, or transforming growth factor-beta (TGF-beta). Present results should help in understanding the basic microglial biology, but also the pathophysiology of activated microglia in neurological diseases such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, stroke, and neurotrauma.
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PMID:Cytokines, chemokines, and cytokine receptors in human microglia. 1211 20

Chitosan is widely used to treat patients with hypoxia-induced diseases such as ischemia, neuronal death, cerebral stroke, and cerebral infarction. Using the ELISA method, we examined the effect of high molecular weight water-soluble chitosan (WSC) on inflammatory cytokine production in the desferrioxamine (DFX, known to mimic hypoxia)-stimulated human mast cell line HMC-1. DFX significantly increased interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared with the control in a time-dependent manner (p<0.05), but did not affect IL-1alpha production and mRNA expression. The increase in IL-6, IL-8, and TNF-alpha levels was significantly inhibited by WSC in a dose-dependent manner with IC(50) values of 0.77, 0.88, and 2.5 microg/ml, respectively. The maximal inhibition rate of IL-6, IL-8, and TNF-alpha production by WSC was 64+/-9.7%, 80+/-9.4% and 54+/-4.5%, respectively. In addition, WSC inhibited DFX-induced activation of nuclear factor (NF)-kappaB. In conclusion, these results suggest that WSC is an inhibitor of NF-kappaB under hypoxic conditions, which might explain its beneficial effect in the treatment of hypoxia-induced inflammatory diseases.
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PMID:Inhibitory effect of high molecular weight water-soluble chitosan on hypoxia-induced inflammatory cytokine production. 1273 19

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).
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PMID:Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke. 1466 35

Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.
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PMID:Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells. 1513 50

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