Tyrosine kinase activation is necessary for inducible nitric oxide synthase
expression by interleukin-1[beta].
Tetsuka, Toshifumi, and Aubrey R. Morrison.
Departments of Medicine and Molecular Biology and Pharmacology, Washington
University School of Medicine, St. Louis, Missouri 63110
APStracts 2:0056C, 1995.
The inflammatory cytokine, interleukin-1 (IL-1), induces the inducible form of
nitric oxide synthase (iNOS) with an increase in NO in rat mesangial cells.
However the cellular mechanisms which underlie the induction of iNOS by IL-
1[beta] in mesangial cells has not been clarified. Since 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) play a central role in IL-1[beta] signaling to induce iNOS in rat
mesangial cells.
Received 11 October 1994; accepted in final form 5 January 1995.
APS Manuscript Number C605-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 27 February 1995.