INTERLEUKIN-1-ALPHA STIMULATES KC SYNTHESIS IN RAT MESANGIAL CELLS - GLUCOCORTICOIDS INHIBIT KC INDUCTION BY IL-1
INTERLEUKIN-1-ALPHA STIMULATES KC SYNTHESIS IN RAT MESANGIAL CELLS - GLUCOCORTICOIDS INHIBIT KC INDUCTION BY IL-1
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DOI：
10.1152/ajprenal.1994.266.5.f713
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发表时间：
1994-05-01
影响因子：
--
通讯作者：
WILSON, CB
中科院分区：
文献类型：
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作者：
FENG, L;XIA, YY;WILSON, CB
为了评估内源性肾小球细胞产生趋化因子在肾小球肾炎炎症产生中的可能作用，从大鼠巨噬细胞cDNA文库中克隆了趋化因子KC。将大鼠KC转染到COS-7细胞中导致中性粒细胞趋化活性增加。KC cDNA在大肠杆菌中以融合蛋白的形式表达，用于产生抗体。利用cDNA衍生的核糖探针和抗体，发现白细胞介素-1 （IL-1）在大鼠系膜细胞中诱导KC的表达。地塞米松可抑制IL-1对KC的诱导。蛋白质合成抑制剂环己亚胺逆转了dex介导的抑制作用，这表明新的蛋白质合成是抑制作用所必需的。核径流分析表明，DEX抑制IL-1诱导的KC转录。DEX的存在没有降低KC mRNA的稳定性。此外，免疫印迹显示，DEX在翻译水平上也抑制了KC的表达。DEX共同抑制KC基因的转录和翻译，有助于降低KC在系膜细胞中的表达。研究发现，系膜细胞对IL-1等促炎细胞因子表达KC，这表明系膜细胞在肾小球炎症中起着趋化源的核心作用。
To assess the possible role of the production of chemokines by intrinsic glomerular cells in the generation of inflammation in glomerulonephritis, the chemokine, KC, was cloned from a rat macrophage cDNA Library. Transfection of rat KC into COS-7 cells resulted in increased neutrophil chemotactic activity. The KC cDNA was expressed as a fusion protein in Escherichia coli for generation of an antibody. By using a riboprobe derived from the cDNA and the antibody, interleukin-1 (IL-1) was found to induce the expression of KC in rat mesangial cells. The induction of KC by IL-1 could be inhibited by dexamethasone (DEX). The protein synthesis inhibitor cycloheximide reversed the DEX-mediated inhibition, which suggested that new protein synthesis was necessary for the inhibitory effect. A nuclear runoff analysis indicated that DEX inhibited the transcription of KC induced by IL-1. The stability of KC mRNA was not decreased in the presence of DEX. Furthermore, immunoblots showed that DEX also inhibited KC expression at the level of translation. Together the inhibition of transcription and translation of the KC gene by DEX contribute to decreased KC expression in mesangial cells. The finding that mesangial cells express KC in response to proinflammatory cytokines, such as IL-1, points to a central role for the mesangial cell as a chemotactic source in glomerular inflammation.