Nitric oxide regulation of IL-8 expression in human endothelial cells.
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.
Villarete
L H
LH
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Remick
D G
DG
D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014471:Umbilical Veins; D014665:Vasodilator Agents / Q000494:pharmacology
D016209:Interleukin-8; D009603:Nitroso Compounds; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester