HUMAN PERITONEAL MESOTHELIAL CELLS SYNTHESIZE IL-1-ALPHA AND IL-1-BETA
HUMAN PERITONEAL MESOTHELIAL CELLS SYNTHESIZE IL-1-ALPHA AND IL-1-BETA
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DOI：
10.1038/ki.1994.359
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发表时间：
1994-10-01
影响因子：
19.6
通讯作者：
CHAIMOVITZ, C
中科院分区：
文献类型：
--
作者：
DOUVDEVANI, A;RAPOPORT, J;CHAIMOVITZ, C
我们研究了人腹膜间皮细胞(HPMC)在脂多糖(LPS)、肿瘤坏死因子α(TNFα)或IL-1α或这三种因子的组合刺激下产生主要的促炎细胞因子IL-1α和-β的能力。用生物法测定IL-1的生物活性，用放射免疫法测定IL-1α和β的水平。我们发现HPMC在这些物质的刺激下能够分泌IL-1α和-β，但内毒素+肿瘤坏死因子α、内毒素+IL-1α或肿瘤坏死因子α+IL-1α的联合刺激对细胞因子的产生有明显的协同作用。所有这三种物质的组合具有显著增强的协同效应。逆转录-聚合酶链式反应发现，IL-1α和β的mRNA水平在刺激后3小时达到峰值。我们发现，内毒素、肿瘤坏死因子α和IL-1α单独或联合作用可引起IL-1α和-βmRNA水平的升高。放线菌素D和放线菌素D阻断IL-1α和β蛋白的产生，提示刺激后需要IL-1的从头产生或mRNA稳定蛋白的合成。因此，我们得出结论：HPMC在腹膜巨噬细胞产生的初始腹膜炎症反应的放大中起重要作用，这些发现对于了解持续非卧床腹膜透析(CAPD)患者的腹膜感染反应具有重要意义。
We studied the ability of human peritoneal mesothelial cells (HPMC) to produce the major pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha) and -beta when stimulated by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or IL-1 alpha, or combinations of these three factors. Biological activity of IL-1 was measured by bioassay, and levels of IL-1 alpha and -beta were determined using specific radioimmunoassays. We found that HPMC are capable of secreting IL-1 alpha and -beta in response to stimulation by these substances, but stimulation with a combination of LPS + TNF alpha, LPS + IL-1 alpha, or TNF alpha + IL-1 alpha, had a marked synergistic effect on cytokine production. A combination of all three substances together had a significantly enhanced synergistic effect. Using reverse transcription PCR, we found a peak in IL-1 alpha and beta mRNA levels three hours after stimulation. We found that LPS, TNF alpha and IL-1 alpha alone, or in combination, caused an increase in IL-1 alpha and -beta mRNA levels. Cycloheximide and actinomycin D blocked the production of IL-1 alpha and -beta protein, showing that de novo production of IL-1 or synthesis of mRNA stabilizing proteins are needed after stimulation. We thus conclude that HPMC play an important role in the amplification of the initial peritoneal inflammatory response which originates in the peritoneal macrophages, and these findings are of importance in understanding the peritoneal response to infection in continuous ambulatory peritoneal dialysis (CAPD) patients.