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

Toshifumi Tetsuka, Dorit Daphna-Iken, Brent W. Miller, Zhonghong Guan, Lisa D. Baier, Aubrey R. Morrison

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156 Scopus citations


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-1β 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-1β-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-1β-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-1β-induced COX-2 mRNA expression. These data indicate a novel interaction between NO and COX pathways.

Original languageEnglish
Pages (from-to)2051-2056
Number of pages6
JournalJournal of Clinical Investigation
Issue number9
StatePublished - May 1 1996


  • cyclic GMP
  • cyclooxygenase
  • interleukin 1
  • nitric oxide
  • prostaglandins


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