Igf-1 and insulin amplify il-1[beta]-induced nitric oxide and prostaglandin biosynthesis implications for the role of igf-1 and insulin in the inflammatory processes. Guan, Zhonghong, Shaavhree Y. Buckman, Lisa D. Baier, and Aubrey R. Morrison. Department of Molecular Biology & Pharmacology and Medicine, Washington University School of Medicine, St. Louis, MO 63110
APStracts 5:0006F, 1998.
The inflammatory cytokine interleukin 1[beta] (IL-1[beta]) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric oxide synthase (iNOS) with concomitant release of prostaglandins (PGs) and nitric oxide (NO) by glomerular mesangial cells._ In our current studies we determine whether insulin and IGF-1 are involved in the signal transduction mechanisms resulting in IL-1[beta] induced-NO and PGE2 biosynthesis in renal mesangial cells. We demonstrate that both insulin and IGF-1 increase IL-1[beta] -induced Cox-2 and iNOS protein expression, which in turn enhance PGE2 and NO production. Our data also indicate that both insulin and IGF-1 enhance IL-1[beta]-induced p38 MAPK phosphorylation and SAPK activation. These findings implicate the possible role of the MAPK pathway in mediating the effects of insulin and IGF-1_ on the upregulation of cytokine stimulated NO and PG biosynthesis. Together, our results indicate that IGF-1 and insulin may function to modulate the renal inflammatory process._

Received 28 July 1997; accepted in final form 5 January 1997.
APS Manuscript Number F250-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 28 January 1998