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Article has an altmetric score of 9

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Referenced in 5 patents
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Research Article Free access | 10.1172/JCI115963

Effects of interferon-gamma on nitric oxide synthase activity and endothelin-1 production by vascular endothelial cells.

S Lamas, T Michel, T Collins, B M Brenner, and P A Marsden

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.

Find articles by Lamas, S. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.

Find articles by Michel, T. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.

Find articles by Collins, T. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.

Find articles by Brenner, B. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.

Find articles by Marsden, P. in: JCI | PubMed | Google Scholar

Published September 1, 1992 - More info

Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):879–887. https://doi.org/10.1172/JCI115963.
© 1992 The American Society for Clinical Investigation
Published September 1, 1992 - Version history
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Abstract

Given the pivotal role suggested for IFN-gamma in immune diseases of the vascular wall, we investigated the effects of IFN-gamma on nitric oxide (NO) and endothelin-1 (ET-1) expression in bovine aortic endothelial cells (BAEC). We have previously reported that TNF-alpha enhanced NO synthase activity in BAEC as assessed by quantifying release of bioactive NO with reporter monolayers and measuring conversion of L-[14C]arginine to L-[14C] citrulline. In murine macrophages IFN-gamma synergizes with TNF-alpha or lipopolysaccharide to induce robust increases in calcium-independent NO synthase activity. In this study we have found that IFN-gamma alone failed to have a significant effect on NO synthase activity in BAEC. In contrast to murine macrophages, IFN-gamma inhibited TNF-alpha-stimulated induction of endothelial NO synthase activity in a concentration-dependent manner. This observation suggests that there is major difference in the response of BAEC and murine macrophages to IFN-gamma. A second major aim of this study was to determine the effect of IFN-gamma on preproET-1 mRNA expression and ET-1 secretion rates in BAEC. IFN-gamma alone had little or no effect on ET-1 mRNA levels and basal ET release when measured for 8 h. However, cotreatment with IFN-gamma potentiated the stimulatory effect of TNF-alpha on BAEC ET-1 mRNA transcript levels and ET release. In contrast, pretreatment of cells with IFN-gamma for 16-24 h blunted the stimulatory effect of TNF-alpha. These findings suggest that endothelial cell expression of vasoactive mediators is modified by the temporal interplay of at least two immune mediators, IFN-gamma and TNF-alpha.

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Referenced in 5 patents
21 readers on Mendeley
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