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)

We examined the effect of ulinastatin in comparison with prednisolone (PSL) and salazosulfapyridine (SASP), well-known drugs for ulcerative colitis (UC), on two experimental UC models induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNB) in rats. Ulinastatin at the doses of 3000 approximately 10,000 units/kg/day (i.v.) significantly ameliorated the formation of erosion and infiltration of inflammatory cells in colonic mucosa in DSS-induced rat UC models. Moreover, ulinastatin at the dose of 10,000 units/kg/day (i.v.) significantly suppressed inflammation with ulcer in the colonic mucosa in TNB-induced rat UC models. PSL at the dose of 1 mg/kg/day (p.o.) also was as effective as ulinastatin on the above two UC models, while SASP at the dose of 100 mg/kg/day (p.o.) was less effective than ulinastatin and PSL. In addition, ulinastatin inhibited the activities of elastase and cathepsin G from human leukocytes, and it suppressed TNF alpha, IL-8 and superoxide production by rat macrophages and rabbit leukocytes in vitro. These results suggest that the suppression of inflammatory mediators produced by leukocytes is involved in the mechanism of the anti-UC action of ulinastatin.
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PMID:[Effects of ulinastatin on experimental ulcerative colitis in rats]. 906 98

Selectin-P expression on platelets stimulated with thrombin was measured in terms of formation of "rosettes" according to Jungi et al. [9]. Selectin-P-mediated platelet/PMNs adhesion was inhibited by iloprost (IC50 = 5.0 nM), sodium nitroprusside (NaNP, IC50 = 0.93 microM) and interleukin-8 (IL-8, IC50 = 88 ng/ml), but activated dose-dependently by oxy-LDL (3-15 micrograms/ml). Glycogen-induced peritonitis in rats up-regulated the iNOS activity measured by the 2,3-[3H]-citrulline formation by the abdominal cavity PMNs up to 6 h after insult. Pretreatment with IL-8 (3 micrograms/300 g iv) decreased the amount of PMNs in ascites as well as its iNOS activity. Chemotaxis mediated iNOS gene expression of PMNs were measured by Northern blot hybridization. IL-8 (100 ng/ml) did not influence the PMNs iNOS gene expression induced by chemotaxis. We conclude that the decrease in iNOS activity by IL-8 involves postranslational modification of the enzyme activity.
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PMID:Influence of oxy-LDL and interleukin-8 on the platelet/PMNs adhesion and on chemotaxis-mediated induction of iNOS in neutrophils. 911 35

The epidermal response to 2 different irritants, nonanoic acid (NAA) and sodium lauryl sulfate (SLS), was investigated with 2 different methods. NAA 80% and SLS 4% were applied under occlusion for up to 24 h. Elemental changes were determined in cryosections by x-ray microanalysis. Compared to unexposed skin a significantly higher sodium/potassium ratio was found after 6 h in NAA-exposed skin and a lower ratio in SLS-exposed. At 24 h both substances had induced similar changes, compatible with a cell injury. The findings demonstrate a time-dependent NAA and SLS response. With reverse transcription polymerase chain reaction, the mRNA expression of interleukin-1 alpha (IL-1 alpha), -1 beta (IL-1 beta), -6 (IL-6), and -8 (IL-8), tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating factor (GM-CSF) in shave biopsies from irritated and unexposed skin was studied at 0. 4. 8 and 24 h. NAA, but not SLS, induced an increase in mRNA expression for IL-6 mRNA-expression for GM-CSF was increased after SLS exposure, but not after NAA. These findings indicate a time and substance dependent difference in the up-regulation of mRNA for different cytokines in epidermis during the first 24 h of the irritant reaction. This might be the effect of differences in the irritants action on the cell membranes, which is also reflected by the differences found in the elemental content at 6 h.
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PMID:Different pathways in irritant contact eczema? Early differences in the epidermal elemental content and expression of cytokines after application of 2 different irritants. 911 30

Most types of cells can produce interleukin (IL)-8 in response to various inflammatory stimuli. To study the role of protein phosphatases in the signal transduction leading to IL-8 production, a subline of HL-60 (C-15) was treated with okadaic acid (OA) and sodium orthovanadate (VA), inhibitors of phosphoserine/phosphothreonine phosphatase and phosphotyrosine phosphatase, respectively. Both OA and VA dramatically increased IL-8 secretion up to 200-fold in the HL-60 cells. OA and VA stimulation was accompanied by a marked increase in IL-8 mRNA expression and also by activation of a transcription factor, NF-kappaB. In addition, an essential role of the NF-kappaB site in the IL-8 gene activation was confirmed by the chloramphenicol acetyltransferase assay. IL-8 production by OA or VA was inhibited by protein kinase inhibitors, including staurosporine, H-7, K252a, herbimycin A, and genistein. Both OA and VA induced significant tyrosine phosphorylation of p44, which was presumed to be Erk1, a member of the mitogen-activated protein kinase family, with concomitant activation of the mitogen-activated protein kinase activity. In parallel, rapid degradation of IkappaB-alpha, an inhibitory component of NF-kappaB, was observed. Since OA-activated Erk1 phosphorylated recombinant IkappaB-alpha in vitro, we assumed that Erk1 is involved in the phosphorylation and subsequent degradation of IkappaB-alpha, thus leading to the activation of IL-8 gene transcription.
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PMID:Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline. Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-kappaB activation. 918 66

Acute Helicobacter pylori infection produces predominantly neutrophilic infiltration of the gastric mucosa. However, the precise mechanisms and mediators of neutrophil migration are not known. Interleukin-8 (IL-8), a potent chemotactic factor for neutrophils, is present at high concentration in the gastric mucosa of subjects with chronic gastritis caused by H. pylori infection. The aims of this study were to determine whether IL-8 stimulates polymorphonuclear leukocyte (PMN) migration across a cultured monolayer of rabbit gastric epithelial cells and whether PMN migration affects epithelial cell barrier function. Confluent gastric epithelial monolayers grown on the inserts were overlaid with PMNs and various amounts of IL-8 were administered into the well under the insert. Gastric epithelial barrier function was assessed by sodium back diffusion. IL-8 stimulated PMN migration across the monolayer in a dose- and time-dependent manner. PMN transmigration significantly increased sodium back diffusion. In conclusion, IL-8 induces PMN migration across a monolayer of cultured gastric epithelial cells. This IL-8 action is associated with impairment of gastric epithelial barrier function. Since H. pylori infection causes a local mucosal increase of IL-8, our present findings may explain the mechanism of H. pylori-induced PMN infiltration of the gastric glands and mucosal injury.
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PMID:Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells. Effect associated with the impairment of gastric epithelial barrier function. 920 Oct 86

A growing family of proteins, known as the chemokines, play an important role in the recruitment and activation of inflammatory cells. The purpose of these studies was to characterize the chemokine receptors present on human sodium butyrate differentiated EoL-3 cells (dEoL-3 cells). Using a combination of 3' rapid amplification of cDNA ends and nested polymerase chain reaction, we detected mRNA for CC chemokine receptor (CCR)1, CCR2, CCR3 and low level of CCR5. Radioligand binding studies demonstrated high-affinity saturable binding for both 125I-macrophage inflammatory protein (MIP)-1alpha and 125I-regulated upon activation normal T cell expressed and secreted (RANTES) with Kd values of 1.4 and 7 nM, respectively. Competition binding with chemokines demonstrated exactly the same rank order of potency for displacement of both ligands: MIP-1alpha approximately monocyte chemoattractant protein (MCP)-3 approximately RANTES > MIP-1beta >> MCP-1 >>> IL-8. RANTES, MCP-3 and MIP-1alpha all produced concentration-dependent transient increases in intracellular calcium concentrations in dEoL-3 cells. Desensitization studies indicated that RANTES, MIP-1alpha and MCP-3 interacted at the same receptor, which is identical in characterization to the cloned CCR1. 125I-MCP-1 also demonstrated high-affinity satuable binding to dEoL-3 cells with a Kd value of 0.4 nM. Competition studies showed that MCP-3 was slightly more potent than MCP-1 and MCP-2. MIP-1alpha, MIP-1beta and RANTES were unable to displace 125I-MCP-1. Addition of either MCP-1 or MCP-3 produced a concentration-dependent elevation of intracellular calcium with a maximun response 2-fold higher than that seen with RANTES or MIP-1alpha. Desensitization studies indicated that MCP-1 and MCP-3 function through CCR2 on these cells. Thus binding and functional studies indicate that dEoL-3 cells express functional CCR1 and CCR2 and that these cells may serve as an important system with which to study the regulation and role of these receptors.
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PMID:Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function. 933 50

The effects of nitric oxide (NO) on human neutrophil chemotactic responses and release of interleukin (IL)-8 was studied. Neutrophils exposed to chemoattractants (IL-8, FMLP, leukotriene B4, and C5a) failed to show increases in intracellular guanosine 3',5'-cyclic monophosphate (cGMP), an indicator of NO production. Although NO increased cGMP in neutrophils, neither of two NO donors (sodium nitroprusside and 3-morpholino-sydonimine) nor a NO synthase inhibitor (N omega-nitro-L-arginine) altered FMLP- or IL-8-elicited neutrophil chemotaxis (P > .25 for all). However, lipopolysaccharide-induced IL-8 production was increased in a dose-dependent manner by a combination of sodium nitroprusside and N-acetylcysteine (P = .03) or by S-nitrosoglutathione (P = .004). NO-augmented IL-8 release was not reproduced by treating neutrophils with dibutyryl-cGMP. Up-regulation of IL-8 release by NO was associated with increased IL-8 mRNA levels (P = .009). These data suggest that NO does not directly affect neutrophil chemotaxis but may indirectly alter chemotactic responses by increasing IL-8 production via a cGMP-independent pathway.
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PMID:Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils. 941 78

Intestinal epithelial (Caco-2) cells secrete the chemokine, IL-8, after stimulation with IL-1beta, but not after lipopolysaccharide. Butyrate is a short chain fatty acid derived from the metabolism of intestinal contents by gut bacteria. Butyrate concentrations reflect, therefore, the bacterial microenvironment established within the intestine. We hypothesized that butyrate may alter the secretion of IL-8 by intestinal epithelial cells in response to stimulation by IL-1beta or lipopolysaccharide. Caco-2 cells were incubated in varying concentrations of sodium butyrate (0-20 mM) for 24 h before stimulation with lipopolysaccharide or IL-1beta. IL-8 secretion was measured over 24 h by ELISA. IL-8 mRNA accumulation was detected by Northern blots. Lipopolysaccharide induced the secretion of IL-8 only after Caco-2 cells cells had been cultured with sodium butyrate. Furthermore, butyrate significantly enhanced IL-8 secretion by cells stimulated with IL-1beta. Butyrate also increased IL-8 mRNA accumulation in stimulated Caco-2 cells. Intestinal epithelial cells can, therefore, be primed by butyrate to become activated by lipopolysaccharide and proinflammatory cytokines. This may represent a mechanism by which intestinal epithelial cells can regulate intestinal inflammation in response to changes in the intestinal milieu.
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PMID:Butyrate enhances interleukin (IL)-8 secretion by intestinal epithelial cells in response to IL-1beta and lipopolysaccharide. 943 17

Recent evidence indicates that free oxygen radicals, in particular hydroxyl radicals, may act as intracellular second messengers for the induction of IL-8, a potent chemoattractant and activator of neutrophil granulocytes. Here we report that peroxynitrite (ONOO-), formed by a reaction of nitric oxide (NO) with superoxide, mediates IL-8 gene expression and IL-8 production in LPS-stimulated human whole blood. The NO synthase inhibitors aminoguanidine and NG-nitro-L-arginine methyl ester (L-NAME) blocked IL-8 release by approximately 90% in response to LPS (1 microg/ml), but did not affect the production of IL-1beta or TNF-alpha. Both aminoguanidine and L-NAME blocked the induction of IL-8 mRNA by LPS. Authentic ONOO- (2.5-80 microM) augmented IL-8 mRNA expression and stimulated IL-8 release in a concentration-dependent manner, whereas the NO-releasing compounds, S-nitroso-N-acetyl-DL-penicillamine and sodium nitroprusside failed to induce cytokine production. Combination of the NO-generating chemicals with a superoxide-generating system (xanthine/xanthine oxidase) markedly increased IL-8 release. Enhanced ONOO- formation was detected in granulocytes, monocytes, lymphocytes, and plasma after challenge with LPS. Furthermore, pyrrolidine dithiocarbamate, an inhibitor of activation of nuclear factor-gammaB, markedly attenuated the induction of IL-8 mRNA expression and IL-8 release by either LPS or ONOO-. Our study identifies ONOO- as a novel signaling mechanism for IL-8 gene expression and suggests that inhibition of ONOO- formation or scavenging ONOO- may represent a novel therapeutic approach to inhibit IL-8 production that could lead to reduction of neutrophil accumulation and activation.
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PMID:Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood. 982 May 46

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on it's conformation in mice. In this study, we examined the relationship between the conformation of Schizophyllan (SPG), a high molecular weight (1-->3)-beta-D-glucan, and cytokine productivity in an in vitro human system. Monocyte-like human cell lines, THP-1 and U-937, and peripheral blood mononuclear cells (PBMC) were used. THP-1 and U-937 cells were differentiated by phorbol myristate acetate (PMA) before use. SPG usually has a triple helical conformation in water, but it was modified by treatment with aqueous sodium hydroxide to become a single helical conformer (SPG-OH). SPG or SPG-OH was added to the macrophage cell culture and gene expression and translation of several cytokines was analyzed by RT-PCR, ELISA, or bioassays. Differentiated THP-1 expressed high levels of cytokine genes, such as IL-8, in response to SPG-OH. High levels of IL-12 p70 were detected from THP-1 cells stimulated with SPG-OH. U-937 cells expressed high levels of IL-8 and TNF-alpha after SPG-OH treatment. Furthermore, PBMC isolated from healthy donors also strongly reacted with SPG-OH but not with SPG. High concentrations of TNF-alpha were detected in SPG-OH-stimulated PBMC cultures. These data suggest that the biological activities of SPG are strongly associated with its conformation in humans.
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PMID:Cytokine synthesis of human monocytes stimulated by triple or single helical conformer of an antitumour (1-->3)-beta-D-glucan preparation, sonifilan. 986 84


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