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)

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
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PMID:Cytokines in inflammatory bowel disease. 952 21

The presence of auto-antibodies and hypergammaglobulinaemia in patients with primary sclerosing cholangitis (PSC) suggest an overactive humoral immune system. Serum cytokines, measured using in-house double monoclonal sandwich ELISA, were used to assess the state of cellular and humoral immunity in this condition by comparison with sex and age matched normal controls and patients with alcoholic cirrhosis (AC). Soluble CD23 (sCD23) as a marker of humoral immunity was significantly elevated in PSC (N = 31) relative to patients with AC (N = 12) and the control group (N = 20) (P < 0.0001 and P < 0.001 respectively). Serum interleukin (IL) 10, as an anti-inflammatory cytokine and IL8, as a marker of neutrophil activation were significantly elevated in patients with PSC relative to those with AC and the controls (P < 0.001 and P < 0.05 respectively). Interferon gamma, as a marker of cellular immunity, and granulocyte-macrophage colony stimulating factor, a marker of monocyte/macrophage function were similar in all the groups. Cytokines and sCD23 were no different between patients with AC and the control group. While more than two thirds of the patients with PSC were positive for ANCA, there was no correlation between the presence of ANCA or ANCA titre and serum levels of either IL8, IL10 and sCD23. These results suggest exaggerated humoral immunity in PSC. The raised levels of IL10 and IL8 in PSC are discussed in the context of inflammatory bowel disease and liver dysfunction.
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PMID:Serum levels of interleukins 8 and 10, interferon gamma, granulocyte-macrophage colony stimulating factor and soluble CD23 in patients with primary sclerosing cholangitis. 954 83

The final composition of leukocytes present in a site of inflammation in response to chemokine stimulation and activation may depend on both the nature of the secreted chemokines as well as the relative expression of the multitude of specific chemokine cell surface receptors on many different cell types. Because related receptors with different affinities and cross-reactive binding capabilities are present on each type of leukocyte, relative differences in receptor distribution and receptor affinity for specific chemokines may significantly influence which cells are ultimately attracted to and activated by each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial cells, LPMNC, and epithelial cells in IBD could establish a chemotactic gradient capable of influencing the increased migration of monocytes/macrophages, granulocytes, and lymphocytes from the blood stream through the endothelium into both the mucosa and submucosa during chronic IBD. The ability of chemokines to induce chemotaxis, leukocyte activation, granule exocytosis, increased production of metalloenzymes, and up-regulation of respiratory burst activity indicates that there may be a variety of different mechanisms by which chemokines could markedly increase chronic inflammation and chronic intestinal tissue destruction in IBD.
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PMID:The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn's disease. 955 29

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

Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn's disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-alpha and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines' serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-gamma mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn's disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-alpha antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn's disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.
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PMID:Cytokines in inflammatory bowel disease. 970 46

To elucidate the possible role of proinflammatory cytokines in inflammatory bowel disease, the expression and localization of interleukin (IL) -6 and IL-8 mRNAs were examined in colonic biopsy specimens obtained from 10 patients with active ulcerative colitis (UC), 5 with inactive UC, 6 with Crohn's disease (CD), and 5 normal controls. In situ hybridization with digoxigenin-labeled probes and immunohistochemistry for both cytokines were performed. The IL-6 mRNA expression was enhanced in the inflamed mucosa in 4 of 6 CD patients, while that of UC patients stayed at baseline. In contrast, IL-8 mRNA expression was apparently augmented (P = 0.044) in 7 of 10 active UC and 3 of 6 CD patients (NS). The cell count positive for IL-8 mRNA per unit area was definitely increased in moderate/severe UC when compared to mild UC (53.1 +/- 14.4/mm2 vs 9.0 +/- 5.1/mm2, P = 0.028) according to the degree of inflammation. IL-6 mRNA positive cells in CD were preferentially located in deeper lamina propria than IL-8 mRNA positive cells in UC. Interestingly, IL-8 mRNA was expressed in the mucosal epithelial cells in one UC patient. The patients treated by corticosteroids tended to show suppressed expression of each mRNA, except one patient with intractable UC. Our data suggest enhanced expression of mucosal IL-6 mRNA in CD and of IL-8 mRNA in UC by infiltrating mononuclear cells, indicating the distinct participation of each cytokine in the pathogenesis of UC and CD. Moreover, intestinal epithelial cells in UC occasionally exhibit IL-8 mRNA.
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PMID:Mucosal expression of interleukin-6 and interleukin-8 messenger RNA in ulcerative colitis and in Crohn's disease. 975 75

Products of an activated immune system may affect cells within the immune system as well as nonlymphoid cells in the local environment. Given the immunologically activated state of the intestinal tract, it is conceivable that locally produced cytokines could regulate epithelial cell function. To assess whether epithelial cells are targets for particular cytokines, we initiated studies on the binding of a panel of proinflammatory cytokines in freshly isolated epithelial cells from normal and inflammatory bowel disease (IBD) patients as well as in cell lines. Isolated intestinal epithelial cells (IEC) were stained with phycoerythrin-conjugated or biotinylated cytokines to determine the expression and density of receptors for IL-1beta, IL-6, granulocyte-macrophage CSF (GM-CSF), and TNF-alpha. Receptors for IL-1beta, IL-6, and GM-CSF were readily detectable in all epithelial cell preparations at levels equal to (GM-CSFR) or lower than those seen on monocytes. However TNFalpha-R were not detectable on freshly isolated IECs. Receptor density was greater in surface vs crypt epithelial cells, but no significant differences were seen between normal and IBD epithelial cells. Expression of IL-1R and IL-6R was enhanced by LPS and IFN-gamma. Functionally, IL-1beta enhanced proliferation of the IEC cell line, DLD1, whereas GM-CSF treatment of de-differentiated crypt-like DLD1 and HT29 cells resulted in enhanced expression of ICAM-1. Furthermore, TNF-alpha treatment enhanced the secretion of IL-8 and GRO-alpha in HT29 cells, but not in freshly isolated IEC cultures. The differential binding and function of proinflammatory cytokines on IEC support the hypothesis that these cytokines may be involved in normal physiological processes as well as in regulating mucosal immune responses.
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PMID:The regulation and functional consequence of proinflammatory cytokine binding on human intestinal epithelial cells. 975 92

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.
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PMID:Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. 988 4

Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected population of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1alpha-induced IL-8 secretion by the colonic epithelial cell line HT-29. We have now explored the C-C chemokine expression and modulation in this system. The combination of TNF-alpha and IFN-gamma was the minimal stimulation required for regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast, IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C chemokine expression is via activation of a wortmannin-sensitive phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial cell chemokine production can be differentially regulated by T cell-derived cytokines and suggest an interplay between epithelial cells and T lymphocytes potentially important in the intestinal inflammation.
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PMID:C-X-C and C-C chemokine expression and secretion by the human colonic epithelial cell line, HT-29: differential effect of T lymphocyte-derived cytokines. 1006 68

Intestinal epithelial cells are able to produce soluble mediators that initiate or amplify inflammatory events in the intestinal mucosa. Interleukin (IL) -8 is suggested to be a cytokine playing a major role during the acute and chronic processes in inflammatory bowel disease (IBD). TH-2 cytokines have been described as down-regulating the inflammatory response. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinal epithelial cells. The human colonic epithelial cell line Caco-2 and freshly isolated intestinal epithelial cells were used. Cells were stimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8 were determined by employing enzyme-linked immunosorbent assay (ELISA). Stimulation with IL-1beta results in a time-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activated epithelial cells resulted in a strong decrease in IL-8 secretion. Maximal inhibition required that TH-2 cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novel findings that IL-4 and IL-13 strongly down-regulate IL-8 secretion from intestinal epithelial cells. A microenvironment containing high concentrations of IL-4 and IL-13 may alter the recruitment of immune cells to enterocytes at least partly by inhibiting IL-8 production. This inhibition might diminish the severity of the intestinal inflammatory response and, thus reduce clinical disease activity.
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PMID:Interleukin (IL)-13 and IL-4 are potent inhibitors of IL-8 secretion by human intestinal epithelial cells. 1008 Jan 64


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