PMID: 7537467Apr 1, 1995Paper

Cytokines activate inducible nitric oxide synthase gene transcription in inner medullary collecting duct cells

The American Journal of Physiology
M G MohauptB C Kone

Abstract

The effects of lipopolysaccharide (LPS) and/or inflammatory cytokines on the expression of inducible nitric oxide synthase (iNOS) were studied in mIMCD-3 cells, derived from the murine inner medullary collecting duct. Under basal conditions, the production of nitrite, a stable metabolite of NO, was negligible; however, incubation with tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IF-gamma) for 24 h resulted in a 12-fold increase in nitrite synthesis and the appearance of abundant iNOS mRNA and protein. The induction of nitrite production and iNOS mRNA was time dependent, requiring approximately 8 h for expression of significant levels of nitrite or iNOS mRNA. Coincubation with the transcription inhibitor actinomycin D or the translation inhibitor cycloheximide prevented the cytokine induction of iNOS mRNA and NO production, indicating that synthesis of intermediary proteins stimulated transcription of the iNOS gene. Nuclear run-on transcription demonstrated that the iNOS gene was transcriptionally inactive under basal conditions, but was markedly induced by TNF-alpha and IF-gamma. These results indicate that inflammatory cytokines stimulate NO production in mIMCD-3 cells by activating iNOS gene transcription in ...Continue Reading

Citations

Jul 18, 2001·American Journal of Physiology. Renal Physiology·T KuncewiczB C Kone
Aug 5, 2000·American Journal of Physiology. Renal Physiology·Z CaiJ S Pollock
Mar 31, 2005·Nitric Oxide : Biology and Chemistry·Chien-Ning HuangTing-Hui Lin

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