Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood - PubMed (original) (raw)

. 1998 Nov 15;161(10):5656-62.

Affiliations

PMID: 9820546

Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood

J G Filep et al. J Immunol. 1998.

Abstract

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.

PubMed Disclaimer

Cited by

Lipoxins: nature's way to resolve inflammation.
Chandrasekharan JA, Sharma-Walia N. Chandrasekharan JA, et al. J Inflamm Res. 2015 Sep 30;8:181-92. doi: 10.2147/JIR.S90380. eCollection 2015. J Inflamm Res. 2015. PMID: 26457057 Free PMC article. Review.
Correlation between change in pulmonary function and suppression of reactive nitrogen species production following steroid treatment in COPD.
Sugiura H, Ichinose M, Yamagata S, Koarai A, Shirato K, Hattori T. Sugiura H, et al. Thorax. 2003 Apr;58(4):299-305. doi: 10.1136/thorax.58.4.299. Thorax. 2003. PMID: 12668791 Free PMC article.
Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression.
Ryan KA, Smith MF Jr, Sanders MK, Ernst PB. Ryan KA, et al. Infect Immun. 2004 Apr;72(4):2123-30. doi: 10.1128/IAI.72.4.2123-2130.2004. Infect Immun. 2004. PMID: 15039334 Free PMC article.
Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline.
Hirano T, Yamagata T, Gohda M, Yamagata Y, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M. Hirano T, et al. Thorax. 2006 Sep;61(9):761-6. doi: 10.1136/thx.200X.058156. Thorax. 2006. PMID: 16936236 Free PMC article. Clinical Trial.
Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-kappa B and AP-1 activation, and IL-8 gene expression in human leukocytes.
József L, Zouki C, Petasis NA, Serhan CN, Filep JG. József L, et al. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13266-71. doi: 10.1073/pnas.202296999. Epub 2002 Sep 16. Proc Natl Acad Sci U S A. 2002. PMID: 12235371 Free PMC article.

Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood - PubMed (original) (raw)