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 examined the effects of the cytokines interleukin 1 (IL-1β) and interleukin 6 (IL-6) on the mitogenesis and proliferation of rat glomerular mesangial cells. Exposure of serum-stimulated cells to IL-1β and IL-6 for 48 hours resulted in a dose- dependent inhibition of both mitogenesis, determined by ³H-thymidine incorporation, and proliferation, determined by absolute cell counts. Both IL-1β and IL-6 stimulated endogenous PGE₂ production in this cell system. Cyclooxygenase inhibition by indomethacin and meclofenamate abrogated the inhibitory effects of both IL-1β and IL-6. Furthermore, addition of exogenous PGE₂ to cytokine-stimulated cells in which cyclooxygenase activity was blocked resulted in inhibition of mitogenesis, while addition of exogenous aracidonic acid to the cytokine-stimulated cells enhanced the induced inhibition of mitogenesis. These results demonstrate that in serum- stimulated mesangial cells, both IL-1β and IL-6 inhibit mitogenesis and proliferation, and that these effects are mediated, in part, by stimulated endogenous prostaglandin production.