AJP - Renal Physiology, Vol 259, Issue 3 419-F424, Copyright © 1990 by American Physiological Society
Cyclooxygenase inhibition enhances rat interleukin 1 beta-induced growth of rat mesangial cells in culture
R. A. Stahl, F. Thaiss, U. Haberstroh, S. Kahf, A. Shaw and W. Schoeppe
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
The cytokine interleukin 1 (IL-1) has growth-promoting activities on
mesangial cells (MC) and enhances MC prostanoid formation. A possible role
of endogenous cyclooxygenase products on IL-1-mediated growth of MC is,
however, unknown. Therefore we evaluated the effect of cyclooxygenase
inhibition on growth of mesangial cells in culture, which were exposed to
DNA recombinant rat interleukin 1 beta (rIL-1 beta). rIL-1 beta increased
[3H]thymidine uptake in MC by approximately 70% after 48 h. This
growth-promoting activity of the cytokine was observed at 1 ng/ml and was
not further enhanced by the increase of the IL-1 beta concentration less
than or equal to 100-fold. IL-1 beta, however, dose dependently stimulated
prostaglandin E2 (PGE2) formation by MC. When prostaglandin synthesis was
inhibited by indomethacin (Indo, 1 microgram/ml), rIL-1 beta (10
ng/ml)-induced cell proliferation was sevenfold greater compared with rIL-1
beta alone. In the presence of Indo (1 microgram/ml), rIL-1 beta (1, 10,
50, and 100 ng/ml) dose dependently stimulated MC proliferation. The
addition of exogenous PGE2 (10(-7) and 10(-8) M) to Indo-treated MC blocked
the mitogenic response of IL-1 beta. We conclude that endogenous PGE2
formation, which is stimulated by IL-1 beta, antagonizes the
growth-promoting activity of the cytokine. PGE2 may thus exert
antiproliferative effects in glomerular diseases, whereas IL-1 might
mediate cell growth.
