Abbott F, Ryan J J, Ceska M, Matsushima K, Sarraf C E, Rees A J
Department of Medicine, Royal Postgraduate Medical School, London, England, United Kingdom.
Kidney Int. 1991 Oct;40(4):597-605. doi: 10.1038/ki.1991.250.
Interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been reported to stimulate human mesangial cells (HMC) to proliferate and synthesize eicosanoids. We have examined whether they also induce HMC to release cytokines. In this study we show that both IL-1 and TNF stimulate HMC to release IL-6 and IL-8. Cycling and quiescent HMC were stimulated with various concentrations of either recombinant IL-1 beta or TNF for 1 to 24 hours. IL-1 beta at doses as low as 6 pg/ml stimulated mesangial cells to synthesize mRNA for both IL-6 and IL-8 as assessed by Northern analysis; mRNA for tubulin remained constant, which demonstrated a specific increase in mRNA. Secretion of IL-6 and IL-8 into the culture medium increased (4.5 to 18 ng/ml and 4 to 40 ng/ml, respectively) measured by ELISAs. TNF had similar effects but only in high concentrations (greater than 100 ng/ml). IL-1 beta did not stimulate cells to proliferate, as measured by 3H thymidine incorporation. TNF caused proliferation but only in concentrations over 100 ng/ml. We conclude that IL-1 beta is a potent stimulator of human mesangial cell production of IL-6 and IL-8, both of which may influence injury in nephritis. TNF also stimulates mesangial cells but only in pharmacological doses.
据报道，白细胞介素-1β（IL-1β）和肿瘤坏死因子（TNF）可刺激人系膜细胞（HMC）增殖并合成类花生酸。我们研究了它们是否也能诱导HMC释放细胞因子。在本研究中，我们发现IL-1和TNF均可刺激HMC释放IL-6和IL-8。用不同浓度的重组IL-1β或TNF刺激处于增殖期和静止期的HMC 1至24小时。通过Northern分析评估，低至6 pg/ml的IL-1β剂量即可刺激系膜细胞合成IL-6和IL-8的mRNA；微管蛋白的mRNA保持恒定，这表明mRNA有特异性增加。通过酶联免疫吸附测定法（ELISA）检测，IL-6和IL-8分泌到培养基中的量增加（分别为4.5至18 ng/ml和4至40 ng/ml）。TNF有类似作用，但仅在高浓度（大于100 ng/ml）时。通过3H胸苷掺入法检测，IL-1β不会刺激细胞增殖。TNF可导致细胞增殖，但仅在浓度超过100 ng/ml时。我们得出结论，IL-1β是人类系膜细胞产生IL-6和IL-8的有效刺激物，这两种细胞因子都可能影响肾炎中的损伤。TNF也可刺激系膜细胞，但仅在药理剂量下。
