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)

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.
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PMID:IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon. 963 33

Fibroblasts are important effector cells having a potential role in augmenting the inflammatory responses in various diseases. In infantile diarrhea caused by enteropathogenic Escherichia coli (EPEC), the mechanism of inflammatory reactions at the mucosal site remains unknown. Although the potential involvement of fibroblasts in the pathogenesis of cryptococcus-induced diarrhea in pigs has been suggested, the precise role of lamina propria fibroblasts in the cellular pathogenesis of intestinal infection and inflammation caused by EPEC requires elucidation. Earlier we reported the lipopolysaccharide (LPS)-induced cell proliferation, and collagen synthesis and downregulation of nitric oxide in lamina propria fibroblasts. In this report, we present the profile of cytokines and adhesion molecules in the cultured and characterized human small intestinal lamina propria fibroblasts in relation to neutrophil migration and adhesion in response to lipopolysaccharide (LPS) extracted from EPEC 055:B5. Upon interaction with LPS (1-10 micrograms/ml), lamina propria fibroblasts produced a high level of proinflammatory mediators, interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and cell adhesion molecules (CAM) such as intercellular cell adhesion molecule (ICAM), A-CAM, N-CAM and vitronectin in a time-dependent manner. LPS induced cell-associated IL-1alpha and IL-1beta, and IL-6, IL-8 and TNF-alpha as soluble form in the supernatant. Apart from ICAM, vitronectin, A-CAM, and N-CAM proteins were strongly induced in lamina propria fibroblasts by LPS. Adhesion of PBMC to LPS-treated lamina propria fibroblasts was ICAM-dependent. LPS-induced ICAM expression in lamina propria fibroblasts was modulated by whole blood, PBMC and neutrophils. Conditioned medium of LPS-treated lamina propria fibroblasts remarkably enhanced the neutrophil migration. The migration of neutrophils was inhibited by anti-IL-8 antibody. Co-culture of fibroblasts with neutrophils using polycarbonate membrane filters exhibited time-dependent migration of neutrophils. These findings indicate that the coordinate production of proinflammatory cytokines and adhesion molecules in lamina propria fibroblasts which do not classically belong to the immune system can influence the local inflammatory reactions at the intestinal mucosal site during bacterial infections and can influence the immune cell population residing in the lamina propria.
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PMID:Interaction of lipopolysaccharide with human small intestinal lamina propria fibroblasts favors neutrophil migration and peripheral blood mononuclear cell adhesion by the production of proinflammatory mediators and adhesion molecules. 1003 24

Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models of H. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.
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PMID:A conventional beagle dog model for acute and chronic infection with Helicobacter pylori. 1033 28

Bacteroides fragilis toxin (BFT) has been shown to be capable of inducing intestinal mucosal inflammation in animals. Such inflammation may be responsible for diarrhoea, which occurs in some, but not all human carriers of enterotoxigenic strains of B. fragilis (ETBF). We have studied responses to BFT by different human intestinal epithelial cell lines and subsequently investigated the expression of IL-8 and TGF-beta by T84 cells. The latter were selected because their responses to BFT, characterized by morphological changes and cell death by apoptosis, were similar to those we have recently observed in primary human colonocytes. We show that BFT dose-dependently increased the expression of transcripts and protein of the polymorphonuclear cell chemoattractant IL-8. BFT also dose-dependently induced the release of TGF-beta, which has been shown to enhance the repair of the injured intestinal epithelium. However, the secreted TGF-beta was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies therefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL-8. BFT-induced release of latent TGF-beta may facilitate the subsequent repair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial cells in vivo could be an important determinant in the development of mucosal disease and symptoms in response to ETBF.
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PMID:Bacteroides fragilis enterotoxin induces the expression of IL-8 and transforming growth factor-beta (TGF-beta) by human colonic epithelial cells. 1069 17

Haemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disorder affecting infants. So far no cases have been reported in Switzerland. It is characterised by the abrupt onset of hyperpyrexia, shock, encephalopathy, diarrhoea, disseminated intravascular coagulation (DIC) and renal and hepatic failure in previously healthy infants. Severe hypoglycaemia has been repeatedly reported in association with HSES. However, the pathophysiology of the hypoglycaemia is not clear. We report on two infants (2 and 7 months old) with typical HSES, both of whom were presented with nonketotic hypoglycaemia. In the first case, plasma insulin was 23 pmol/l at the time of hypoglycaemia (0.1 mmol/l). In the second case, increased values for interleukin-6 (IL-6) (319 pg/ml) and IL-8 (1382 pg/ml) were found 24 hours after admission, whereas IL-1 and tumour necrosis factor-alpha (TNF-alpha) were not measurable. Alpha-1-antitrypsin was decreased (0.6 g/l). In hyperpyrexic, unconscious and shocked infants, HSES should be considered and hypoglycaemia should be specifically looked for. Hypoglycaemia is not caused by hyperinsulinism but may be secondary to the release of cytokines.
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PMID:Haemorrhagic shock and encephalopathy syndrome: report of two cases with special reference to hypoglycaemia. 1070 Dec 32

The objective of this study was to identify parameters indicating a risk for developing typical haemolytic uremic syndrome (D+HUS) during the prodromal phase of diarrhea caused by enterohaemorrhagic Escherichia coli (EHEC). Forty-eight children were studied prospectively with regard to inflammatory serum factors on admission to hospital. Ten patients developed D+HUS (group I), 15 suffered from viral-gastroenteritis (group IIa) and 23 from other types of bacterial gastroenteritis (group IIb). Mean levels of IL-8 tended to be elevated in group I compared to groups IIa and IIb. Neopterin and IL-10 levels particularly were significantly decreased in HUS in comparison to both gastroenteritis groups. Low IL-10 levels indicate a substantial disregulation of the immune response in HUS, as IL-10 downregulates the pro-inflammatory response and suppresses pro-coagulant activity in experimental endotoxemia. Our results suggest low neopterin, high IL-8 and especially low IL-10 levels are indicators of a high risk for developing HUS.
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PMID:Inflammatory and immunological parameters in children with haemolytic uremic syndrome (HUS) and gastroenteritis-pathophysiological and diagnostic clues. 1084 73

Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. EAEC infections are associated with intestinal inflammation and growth impairment in infected children, even in the absence of diarrhea. We previously reported that prototype EAEC strains rapidly induce IL-8 production by Caco-2 intestinal epithelial cells, and that this effect is mediated by a soluble, heat-stable factor released by these bacteria in culture. We herein report the cloning, sequencing, and expression of this biologically active IL-8-releasing factor from EAEC, and its identification as a flagellin that is unique among known expressed proteins. Flagella purified from EAEC 042 and several other EAEC isolates potently release IL-8 from Caco-2 cells; an engineered aflagellar mutant of 042 does not release IL-8. Finally, cloned EAEC flagellin expressed in nonpathogenic E. coli as a polyhistidine-tagged fusion protein maintains its proinflammatory activity. These findings demonstrate a major new means by which EAEC may cause intestinal inflammation, persistent diarrhea, and growth impairment that characterize human infection with these organisms. Furthermore, they open new approaches for diagnosis and vaccine development. This novel pathogenic mechanism of EAEC extends an emerging paradigm of bacterial flagella as inflammatory stimuli.
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PMID:Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells. 1113 75

This study was conducted to investigate the efficacy of rebamipide against experimental colitis induced by dextran sulfate sodium (DSS) in a rat model of inflammatory bowel disease. Experimental colitis was induced in male Wistar rats by oral administration of 3% DSS solution for one week. The rats were provided with standard diet containing 0.105% rebamipide (160 mg/kg/day) for 1 week. In rats treated with rebamipide, clinical (body weight loss, bloody diarrhea, reduced physical activity, severe anemia, shortened colonic length, and perianal injury) and histopathological (pathological lesion score) findings of DSS colitis were significantly less than in rats with DSS colitis not treated with rebamipide. Rebamipide thus inhibited the induction of colitis. Rebamipide significantly reduced concentrations of both interleukin-1alpha and GRO/CINC-1 (IL-8-like substance) and cell infiltrates in colonic wall, in parallel with decreased activity of myeloperoxidase. It also reduced expression of IL-1 mRNA but did not influence expression of GRO/CINC-1 mRNA. The attenuation of colonic indices of colitis by rebamipide in this rat model suggests that this drug might have beneficial effects in the treatment of human ulcerative colitis. These effects of rebamipide are attributable to its inhibition of inflammatory cytokine-mediated granulocyte (neutrophil) infiltration into the colon.
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PMID:Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats. 1100 13

Cryptosporidium parvum is a common cause of diarrhea in humans. Although mild inflammatory mucosal infiltrate is usually observed, limited information is currently available on the pathogenic mechanisms involved in this phenomenon. The aim of this work was to investigate in vitro the influence of C. parvum infection on the secretion of lymphocyte-targeted chemokines (RANTES. MIP-1alpha, MIP-1beta, IL-8), proinflammatory cytokines (TNF-alpha, GM-CSF and IL-6) and TGF-beta by human enterocytic Caco-2 cells. C. parvum infection stimulates IL-8, RANTES and TGF-beta secretion by both the basal and apical side of caco-2 cells. A slight increase in TNF-alpha production by infected cells was observed in the apical compartment. Data suggest that enterocytic chemokines and/or TGF-beta are involved in the initiation and regulation of the mucosal response to C. parvum infection.
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PMID:Cryptosporidium parvum infection stimulates the secretion of TGF-beta, IL-8 and RANTES by Caco-2 cell line. 1113 8

When epithelial cells first encounter cholera toxin (Ctx) produced by Vibrio cholerae they secrete not only chloride ions responsible for causing diarrhoea, but also a number of cytokines that may contribute to the toxin's potent immunomodulatory properties. Much less is known about the ability of the heat-labile enterotoxin of Escherichia coli (Etx), a close homologue of Ctx, to elicit cytokine secretion by epithelial cells. This study shows that treatment of human intestinal epithelial T84 cells with Etx induces expression of IL-6, IL-10, IL-1R antagonist, as well as IL-1alpha and IL-1beta and low levels of IL-8. Such induction was totally dependent on the intrinsic ADP-ribosylating activity of the toxin A-subunit, and could be mimicked by cAMP-elevating agents, such as forskolin and dibutyryl cAMP. By comparison, neither an enzymically inactive mutant of Etx nor EtxB was able to induce cytokine secretion. The behaviour of Ctx and CtxB was very similar to that of Etx and EtxB, respectively. The spectrum of cytokines released by Etx and Ctx indicates that the toxins may create a local microenvironment that strongly biases the immune response towards an anti-inflammatory and a polarized Th2 response.
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PMID:Contribution of the ADP-ribosylating and receptor-binding properties of cholera-like enterotoxins in modulating cytokine secretion by human intestinal epithelial cells. 1188


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