CYTOKINE STIMULATION OF PROSTAGLANDIN PRODUCTION INHIBITS THE PROLIFERATION OF SERUM-STIMULATED MESANGIAL CELLS

Mesangial cell proliferation contributes to glomerulosclerosis and is associated with the development of end-stage renal disease. We examine d the effects of the cytokines interleukin 1 (IL-1beta) and interleuki n 6 (IL-6) on the mitogenesis and proliferation of rat glomerular mesa ngial cells. Exposure of serum-stimulated cells to IL-1beta and IL-6 f or 48 hours resulted in a dose-dependent inhibition of both mitogenesi s, determined by H-3-thymidine incorporation, and proliferation, deter mined by absolute cell counts. Both IL-1beta and IL-6 stimulated endog enous PGE2 production in this cell system. Cyclooxygenase inhibition b y indomethacin and meclofenamate abrogated the inhibitory effects of b oth IL-1beta and IL-6. Furthermore, addition of exogenous PGE2 to cyto kine-stimulated cells in which cyclooxygenase activity was blocked res ulted in inhibition of mitogenesis, while addition of exogenous aracid onic acid to the cytokine-stimulated cells enhanced the induced inhibi tion of mitogenesis. These results demonstrate that in serum-stimulate d mesangial cells, both IL-1beta and IL-6 inhibit mitogenesis and prol iferation, and that these effects are mediated, in part, by stimulated endogenous prostaglandin production.