Cyclooxygenase inhibition enhances rat interleukin 1 beta-induced growth of rat mesangial cells in culture.
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.
Stahl
R A
RA
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Thaiss
F
F
Haberstroh
U
U
Kahf
S
S
Shaw
A
A
Schoeppe
W
W
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000254:growth & development*; D006207:Half-Life; D007375:Interleukin-1 / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D015232:Dinoprostone