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)

The effect of interleukin(IL)-8 and leukotriene B4 (LTB4) on the induction of nitric oxide (NO) synthase in rat peritoneal neutrophils (PMN) ex vivo was studied. IL-8, but not LTB4, caused concentration-dependent inhibition of the induction of a Ca(2+)-independent NO synthase ex vivo. The effect of IL-8 was not attributable to the synthesis of an inhibitor of this enzyme. These findings suggest complex regulatory control of the induction of NO synthase by cytokines.
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PMID:Interleukin-8 inhibits the induction of nitric oxide synthase in rat peritoneal neutrophils. 137 4

Human monocytes (M phi) require stimulation with substances such as bacterial endotoxin [LPS (lipopolysaccharide)] to produce angiogenic activity. In this study, we report that stimulation of M phi with LPS (5 micrograms/ml) in the absence of L-arginine greatly reduced their production of angiogenic activity, as assessed in vivo in rat corneas and in vitro by chemotaxis of human umbilical vein endothelial cells (HU-VECs). D-Arginine did not substitute for L-arginine in the production of angiogenic activity. The nitric oxide synthase (NO synthase, EC 1.14-13.39) inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) both inhibited the production of angiogenic activity by LPS-stimulated M phi in the presence of L-arginine, suggesting the involvement of this enzyme in the pathway that generates angiogenic activity. Neither of these substances directly inhibited the M phi-derived angiogenic activity. LPS-induced production of the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8) was not significantly reduced when M phi were incubated in the absence of L-arginine. Similarly, L-NMMA and L-NAME did not significantly reduce the LPS-induced production of these cytokines by M phi in the presence of L-arginine. These results suggest that the LPS-stimulation-dependent generation of angiogenic activity by M phi requires an L-arginine-dependent NO-synthase effector mechanism that may be independent of the generation of TNF-alpha and IL-8.
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PMID:Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. 751 98

The production of nitric oxide (NO) is increased in experimental nephritis, with NO thought to be an important mediator of cell damage. The cytokines interleukin 1 beta (IL-1 beta), IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) are released from mesangial cells in vitro or are expressed in various forms of glomerulonephritis. We investigated the effects of these cytokines on NO synthesis in cultured rat mesangial cells. Incubation of mesangial cells with IL-1 beta (10 ng/ml) for 24 h increased the accumulation of NO and guanosine 3',5'-cyclic monophosphate (cGMP). IL-6, IL-8, MCP-1 and TGF-beta showed no significant effect on the production of NO or cGMP. Transcripts of the inducible NO synthase (iNOS) gene were not detected in unstimulated mesangial cells. However, exposure of cells to IL-1 beta (10 ng/ml) for 24 h resulted in the appearance of iNos mRNA. IL-1 beta-induced NO synthesis was significantly inhibited by NG-monomethyl-L-arginine, cycloheximide, actinomycin D, dexamethasone, and TGF-beta. These results indicate that, of the various cytokines studied, only IL-1 beta stimulates iNOS mRNA accumulation and NO synthesis in mesangial cells. NO may function in an autocrine manner to modulate the glomerular response to inflammation.
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PMID:Nitric oxide synthesis in rat mesangial cells induced by cytokines. 753 90

The effect of cytokines, growth factors, mitogens, and bacterial products on nitric oxide (NO) generation by monolayers of small intestinal epithelial cells-6 (IEC-6) cells was evaluated. Subconfluent IEC-6 cells were maintained in DMEM containing 5% fetal calf serum and after 16-24 hr of incubation, the medium was replaced with fresh medium in the presence or absence of calcium ionophore (CaI), L-NAME, L-NNA, individual growth factors, cytokines, or mitogens. After 72 hr of culture, the media supernatant was collected and NO chi generation was determined. NO synthase activity was determined in sonicated supernatants of IEC-6 cells by [14C] arginine conversion to citrulline. NO chi generation in subconfluent cultures was greater than in fully confluent cultures, suggesting contact inhibition. NO chi generation by IEC-6 cells was significantly increased by CaI and inhibited by L-NAME and L-NNA. LPS, IL-1 beta, IL-2, IL-8, IFN-8, TFN-alpha, EGF, TGF-alpha, bFGF, and PHA significantly increased NO chi generation. NO synthase activity in IEC-6 cells (4.2 +/- 1.7 pmol/min/10(6) cells) was NADPH dependent. These results suggest that stimulation of NO chi generation by intestinal epithelial cells through cytokine bacterial products and mitogens may be one of the mechanisms responsible for their effects in the intestinal tract.
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PMID:NO chi generation by cultured small intestinal epithelial cells. 755 34

The regulatory signals required to induce the production of IL-8, an important neutrophil chemoattractant and activator, have yet to be clearly defined. We examined the role of nitric oxide (NO) in IL-8 regulation. The NO synthase inhibitor, (L)-NG-nitroarginine methyl ester (L-NAME), inhibited the TNF-stimulated IL-8 production in the human endothelial cell line, ECV304, in a dose-dependent manner without affecting cellular viability (TNF alone, 5.5 +/- 0.9 ng/ml; TNF + 5 mM L-NAME, 2.4 +/- 0.5 ng/ml). Moreover, exogenously added NO produced by the spontaneous NO generating compounds, S-Nitroso-N-acetyl-D,L-pennicillamine (SNAP) and Ethanamine, 2,2'-(hydroxynitrosohydrazono)bis- (DETA NONOate), induced a dose-dependent release of IL-8 from these cells. Maximal stimulation of IL-8 was found to be 1.2 +/- 0.1 ng/ml with the 1 mM concentration of SNAP and 1.6 +/- 0.1 ng/ml with the 2 mM concentration of DETA NONOate. These results provide key evidence substantiating a regulatory role of NO in IL-8 expression.
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PMID:Nitric oxide regulation of IL-8 expression in human endothelial cells. 779 82

We confirmed that iloprost is very potent in preserving the deformability of rabbit red blood cells (RBC). Incubation of RBC with a small number (up to 1.2 x 10(6) cells/ml) of polymorphonuclear leukocytes (PMNs) caused a gradual decline in RBC deformability. The addition of PMNs up to 2.8 x 10(6) cells/ml increased RBC deformability but, at higher concentrations, both in the presence and absence of a neutrophil activating cytokine (interleukin-8; IL-8), PMNs reduced the deformability of RBCs. In the presence of a small number of PMNs, the deformability of RBC was increased by nitric oxide (NO) donors, such as sydnonimine (SIN-1) or sodium nitroprusside, and reduced by the NO synthase inhibitor, NG-monomethyl-L-arginine. We suggest that the deformability of RBC is modulated by PMNs via the release of NO and that the NO concentration is of critical importance in this modulatory mechanism. NO seems to preserve or enhance RBC deformability within a certain range of concentrations, but these effects are reversed or eliminated at both too low and too high concentrations.
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PMID:Nitric oxide from polymorphonuclear leukocytes modulates red blood cell deformability in vitro. 847 57

1. The effect of systemic treatment of mice with murine recombinant interleukin-4 (IL-4) or interleukin-10 (IL-10) on neutrophil infiltration into a specific tissue site and nitric oxide (NO) production from peritoneal macrophages was investigated. 2. Intravenously (i.v.) administered IL-4 (0.01-10 micrograms per mouse, approximately 0.3-300 micrograms kg-1, i.v.) and IL-10 (0.01-1 micrograms per mouse, approximately 0.3-30 micrograms kg-1, i.v.) dose-dependently inhibited neutrophil accumulation into a 6-day-old murine air-pouch induced by local application of interleukin-1 beta (IL-1 beta, 5 ng), with approximate ED50s of 0.35 and 0.90 micrograms, respectively. Neither IL-4 (1 micrograms, 30 micrograms kg-1, i.v.) nor IL-10 (1 micrograms, 30 micrograms kg-1, i.v.) prevented leucocyte accumulation in the mouse air-pouches when interleukin-8 (IL-8, 1 micrograms) was used as chemoattractant. Similarly, neither cytokine had any effect on the in vitro up-regulation of CD11b antigen on the surface of murine circulating neutrophils. 3. Treatment of mice with lipopolysaccharide (LPS, 0.3 mg kg-1, i.p.) caused an increase in the formation of NO (measured as nitrite accumulation) in the supernatant of peritoneal macrophages ex vivo. Pretreatment of mice with IL-4 (0.01-1 micrograms i.v., 20 min before LPS), but not with IL-10 (1 micrograms i.v., 20 min before LPS), caused a dose-dependent reduction in this LPS-stimulated formation of nitrite by peritoneal macrophages ex vivo. 4. Activation of murine macrophages with LPS (1 microgram ml-1 for 24 h) in vitro caused a significant increase in nitrite release in the supernatant of these cells. Pretreatment of either J774.2 or peritoneal macrophages with IL-4 (0.1-1 microg ml-1, 20 min before LPS), but not with IL-1O (1 microg ml', 20 min before LPS) caused a concentration-related attenuation of this LPS-stimulated nitrite formation.5 Thus, both IL-4 and IL-10 inhibit the migration of leucocytes (stimulated by IL-1beta>) in vivo; IL-4 (but not IL-10) inhibits the induction of NO synthase caused by LPS in murine macrophages in vitro and ex vivo.
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PMID:Effect of interleukin-4 and interleukin-10 on leucocyte migration and nitric oxide production in the mouse. 856 56

While the regulation of nitric oxide (NO) by inflammatory cytokines or lipopolysaccharide (LPS) has received considerable attention, NO modulation of cytokine expression has yet to be fully explored. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited interleukin (IL)-8 and IL-6 production in LPS-stimulated human whole blood in a dose-dependent manner. In the presence of 1 microgram/mL LPS, L-NAME blocked IL-8 release (72 +/- 4% inhibition at 20 mM (mean +/- SEM, p < .05)) 24 h post-LPS without affecting cellular viability. IL-6 production was significantly inhibited only with the highest dose of L-NAME used. L-NAME inhibition of IL-8 production was also observed at the mRNA level. Conversely, direct exposure of whole blood to NO with the spontaneous NO liberator DETA NONOate caused a dose-dependent stimulation of IL-8, but had no effect on IL-6 release. IL-8 concentrations rose from 8.3 +/- 1.9 ng/mL at 24 h to 31.7 +/- 7.6 ng/mL at 72 h with a single stimulation of 10 mM DETA NONOate. The hydroxyl radical scavenger dimethyl sulfoxide (DMSO) prevented the DETA NONOate induction of IL-8, suggesting the participation of the hydroxyl radical in the NO-induced IL-8 production. These results provide important evidence substantiating a role for NO as a regulator of cytokine expression.
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PMID:Nitric oxide regulation of interleukin-8 gene expression. 898 33

Interleukin-8 (IL-8) and nitric oxide (NO) may be important mediators in the pathogenesis of chronic idiopathic inflammatory bowel disease (CIIBD), but their roles in disease activity in ulcerative colitis (UC) and Crohn's disease (CD) are uncertain. The aim of this study was to measure mRNA for IL-8 and inducible NO synthase (iNOS) in small mucosal biopsies from untreated patients at first presentation and to relate these measurements to the histological levels of polymorph infiltration graded on a ten-point scale. For this purpose, a sensitive enzyme-linked oligonucleotide chemiluminescent assay (ELOCA) was developed to quantitate reverse transcription-polymerase chain reaction (RT-PCR) products amplified from RNA from paired biopsy samples. The levels of IL-8 and iNOS mRNAs were calculated as ratios of the RT-PCR products to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RT-PCR product. In UC patients, median values of IL-8/GAPDH and iNOS/GAPDH were significantly elevated compared with controls and CD. However, in both UC and CD, the IL-8/GAPDH and iNOS/GAPDH ratios correlated significantly with polymorph infiltration. ELOCA enabled quantitation of multiple mRNAs in small mucosal biopsies from untreated patients with CIIBD and supported a role for IL-8 and iNOS in acute inflammation in both UC and CD.
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PMID:Interleukin-8 and inducible nitric oxide synthase mRNA levels in inflammatory bowel disease at first presentation. 907 8

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
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PMID:Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. 907 23


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