Tyrosine kinase activation is necessary for inducible nitric oxide synthase expression by interleukin-1 beta

Am J Physiol. 1995 Jul;269(1 Pt 1):C55-9. doi: 10.1152/ajpcell.1995.269.1.C55.


The inflammatory cytokine interleukin-1 (IL-1) induces the inducible form of nitric oxide synthase (iNOS) with an increase in nitric oxide in rat mesangial cells. However, the cellular mechanisms that underlie the induction of iNOS by IL-1 beta in mesangial cells has not been clarified. Because we have shown that tyrosine kinase inhibitors attenuate IL-1 beta-induced cyclooxygenase expression and prostaglandin production, we investigated the effect of tyrosine kinase inhibitors on IL-1 beta-induced nitrite production and iNOS mRNA expression in rat mesangial cells. The tyrosine kinase inhibitors genistein and herbimycin A attenuated IL-1 beta-induced nitrite production in a dose-dependent manner. In addition, both of these inhibitors blocked IL-1 beta-induced iNOS mRNA expression. These data suggest that tyrosine kinase(s) plays a central role in IL-1 beta signaling to induce iNOS in rat mesangial cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Benzoquinones
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Induction
  • Genistein
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / enzymology
  • Interleukin-1 / pharmacology*
  • Isoflavones / pharmacology
  • Lactams, Macrocyclic
  • Male
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Quinones / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Rifabutin / analogs & derivatives


  • Benzoquinones
  • Interleukin-1
  • Isoflavones
  • Lactams, Macrocyclic
  • Quinones
  • RNA, Messenger
  • Recombinant Proteins
  • Rifabutin
  • Nitric Oxide
  • herbimycin
  • Genistein
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Protein-Tyrosine Kinases