Nitric oxide amplifies interleukin 1-induced cyclooxygenase-2 expression in rat mesangial cells

Interleukin 1 and nitric oxide (NO) from infiltrating macrophages and activated mesangial cells may act in concert to sustain and promote glomerular damage. To evaluate if such synergy occurs, we evaluated the effect if IL-1 beta and NO on the formation of prostaglandin (PG)E2 and cyclooxygenase (CO...

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Bibliographic Details
Published in:The Journal of clinical investigation 1996-05, Vol.97 (9), p.2051-2056
Main Authors: Tetsuka, T, Daphna-Iken, D, Miller, B W, Guan, Z, Baier, L D, Morrison, A R
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cyclooxygenase 2
Dinoprostone - biosynthesis
Drug Synergism
Gene Expression Regulation, Enzymologic - drug effects
Glomerular Mesangium - metabolism
Humans
Interleukin-1 - pharmacology
Isoenzymes - biosynthesis
Male
Membrane Proteins
Nitric Oxide - pharmacology
Prostaglandin-Endoperoxide Synthases - biosynthesis
Rats
Rats, Sprague-Dawley
Signal Transduction - drug effects
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Summary:Interleukin 1 and nitric oxide (NO) from infiltrating macrophages and activated mesangial cells may act in concert to sustain and promote glomerular damage. To evaluate if such synergy occurs, we evaluated the effect if IL-1 beta and NO on the formation of prostaglandin (PG)E2 and cyclooxygenase (COX) expression. The NO donors, sodium nitroprusside and S-nitroso-N-acetylpenicillamine, alone did not increase basal PGE2 formation. However, these compounds amplified IL-1 beta-induced PGE2 production. Similarly, sodium nitroprusside and S-nitroso-N-acetylpenicillamine by themselves did not induce mRNA and protein for COX-2, the inducible isoform of COX; however, they both potentiated IL-1 beta-induced mRNA and protein expression of COX-2. The stimulatory effect of NO is likely to be mediated by cGMP since (a) an inhibitor of the soluble guanylate cyclase, methylene blue, reversed the stimulatory effect of NO donors on COX-2 mRNA expression; (b) the membrane-permeable cGMP analogue, 8-Br-cGMP, mimicked the stimulatory effect of NO donors on COX-2-mRNA expression; and (c) atrial natriuretic peptide, which increases cellular cGMP by activating the membrane-bound guanylate cyclase, also amplified IL-1 beta-induced COX-2 mRNA expression. These data indicate a novel interaction between NO and COX pathways.
ISSN:0021-9738
DOI:10.1172/jci118641