Cyclooxygenase inhibition enhances rat interleukin 1 beta-induced growth of rat mesangial cells in culture

Am J Physiol. 1990 Sep;259(3 Pt 2):F419-24. doi: 10.1152/ajprenal.1990.259.3.F419.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cells, Cultured
  • Cyclooxygenase Inhibitors*
  • Dinoprostone / biosynthesis
  • Dinoprostone / pharmacology
  • Glomerular Mesangium / growth & development*
  • Half-Life
  • Interleukin-1 / physiology*
  • Prostaglandins / pharmacology
  • Rats
  • Recombinant Proteins

Substances

  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Prostaglandins
  • Recombinant Proteins
  • Dinoprostone