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PMID: 1381725 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 90 ·No. 3 ·1992-09-00 ·Pages 879-87

Lamas S, Michel T, Collins T, Brenner BM, Marsden PA

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.

MeSH Terms
Amino Acid Oxidoreductases/analysis Animals Arginine/metabolism Cattle Cells, Cultured Citrulline/biosynthesis Endothelins/biosynthesis Endothelium, Vascular/metabolism Interferon-gamma/pharmacology Nitric Oxide Synthase Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Endothelins Tumor Necrosis Factor-alpha Citrulline Interferon-gamma Arginine Nitric Oxide Synthase Amino Acid Oxidoreductases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lamas S
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02114.
Michel T
Collins T
Brenner B M
Marsden P A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115963
Published
1992-09-00
Pages
879-87
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC329942
Subset
IM
Grants
NIDDK NIH HHS · DK-35930 · United States
External Links
PubMed source DOI: 10.1172/JCI115963 PMC Full Text View journal details
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