Stahl R A, Thaiss F, Haberstroh U, Kahf S, Shaw A, Schoeppe W
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Am J Physiol. 1990 Sep;259(3 Pt 2):F419-24. doi: 10.1152/ajprenal.1990.259.3.F419.
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.
细胞因子白细胞介素1（IL-1）对系膜细胞（MC）具有促生长活性，并能增强MC类前列腺素的生成。然而，内源性环氧化酶产物在IL-1介导的MC生长中可能发挥的作用尚不清楚。因此，我们评估了环氧化酶抑制对培养的系膜细胞生长的影响，这些细胞暴露于DNA重组大鼠白细胞介素1β（rIL-1β）。48小时后，rIL-1β使MC中[3H]胸腺嘧啶核苷摄取增加约70%。在1 ng/ml时可观察到这种细胞因子的促生长活性，且当IL-1β浓度增加至100倍及以下时，其促生长活性并未进一步增强。然而，IL-1β能剂量依赖性地刺激MC合成前列腺素E2（PGE2）。当用吲哚美辛（Indo，1μg/ml）抑制前列腺素合成时，rIL-1β（10 ng/ml）诱导的细胞增殖比单独使用rIL-1β时高7倍。在存在Indo（1μg/ml）的情况下，rIL-1β（1、10、50和100 ng/ml）剂量依赖性地刺激MC增殖。向用Indo处理的MC中添加外源性PGE2（10^-7和10^-8 M）可阻断IL-1β的促有丝分裂反应。我们得出结论，由IL-1β刺激产生的内源性PGE2形成拮抗了该细胞因子的促生长活性。因此，PGE2可能在肾小球疾病中发挥抗增殖作用，而IL-1可能介导细胞生长。
