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-1 beta) and interleukin 6 (IL-6) on the mitogenesis and proliferation of rat glomerular mesangial cells. Exposure of serum-stimulated cells to IL-1 beta 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-1 beta and IL-6 stimulated endogenous PGE2 production in this cell system. Cyclooxygenase inhibition by indomethacin and meclofenamate abrogated the inhibitory effects of both IL-1 beta 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-1 beta and IL-6 inhibit mitogenesis and proliferation, and that these effects are mediated, in part, by stimulated endogenous prostaglandin production.
Matsell
D G
DG
Department of Pediatrics, University of Western Ontario, London, Canada.
Gaber
L W
LW
Malik
K U
KU
D000818:Animals; D001790:Blood Physiological Phenomena; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D008469:Meclofenamic Acid; D015232:Dinoprostone; D013936:Thymidine; D007213:Indomethacin