PMID: 7514363Apr 1, 1994Paper

Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells

The American Journal of Physiology
D Beasley, M Eldridge

Abstract

Cytokine-inducible nitric oxide (NO) production has been implicated in the pathogenesis of septic shock. The present study was designed to determine which cytokines induce expression of the NO synthase gene in rat aortic vascular smooth muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1 beta), and levels continued to increase up to 24 h. Levels of NO synthase transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1 nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by release of nitrite, conversion of L-arginine to L-citrulline, and increased levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and interferon-gamma were ineffective. IL-1 beta was more potent and effective than TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO synthase mRNA was present in aorta from rats 6 h after treatment...Continue Reading

Citations

Mar 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·S SasuD Beasley
May 26, 2005·Circulation Journal : Official Journal of the Japanese Circulation Society·Parin SuwannapraphaYaowapa Maneerat
Dec 18, 2001·American Journal of Physiology. Cell Physiology·Xingwu TengJohn D Catravas
Feb 27, 2004·American Journal of Physiology. Cell Physiology·Natasha C BrownerThomas M Lincoln

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