Matsell D G, Gaber L W, Malik K U
Department of Pediatrics, University of Western Ontario, London, Canada.
Kidney Int. 1994 Jan;45(1):159-65. doi: 10.1038/ki.1994.19.
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.
系膜细胞增殖会导致肾小球硬化，并与终末期肾病的发展相关。我们研究了细胞因子白细胞介素1（IL-1β）和白细胞介素6（IL-6）对大鼠肾小球系膜细胞有丝分裂和增殖的影响。将血清刺激的细胞暴露于IL-1β和IL-6 48小时，导致通过3H-胸腺嘧啶核苷掺入确定的有丝分裂和通过绝对细胞计数确定的增殖均呈剂量依赖性抑制。在该细胞系统中，IL-1β和IL-6均刺激内源性前列腺素E2的产生。吲哚美辛和甲氯芬那酸对环氧化酶的抑制消除了IL-1β和IL-6的抑制作用。此外，向环氧化酶活性被阻断的细胞因子刺激细胞中添加外源性前列腺素E2导致有丝分裂抑制，而向细胞因子刺激细胞中添加外源性花生四烯酸增强了诱导的有丝分裂抑制。这些结果表明，在血清刺激的系膜细胞中，IL-1β和IL-6均抑制有丝分裂和增殖，并且这些作用部分是由刺激的内源性前列腺素产生介导的。
