白细胞介素10抑制核因子kB介导的肾小管上皮细胞表达细胞间黏附分子1  

Inhibitory effect of IL-10 on induced expression of ICAM-l in renal tubular cells is mediated by down regulated activity of nuclear factor kB

作　　者：陈建粮[1] 李晓玫[1] 王海燕[1] 

机构地区：[1]北京医科大学第一医院肾内科,100034

出　　处：《中华肾脏病杂志》2000年第1期16-19,共4页Chinese Journal of Nephrology

基　　金：国家自然科学基金!(39570298)

摘　　要：目的研究白细胞介素１０（ＩＬ－１０）对人近端肾小管上皮细胞（ＨＫ－２细胞）在促炎症因子肿瘤坏死因子α（ＴＮＦα）作用下表达细胞间黏附分子１（ＩＣＡＭ－ｌ）及其相关核转录途径的影响。方法 用ＨＫ－２细胞作靶细胞，用细胞酶联免疫吸附法（ＥＩＪＳＡ）和Ｎｏｒｔｈｅｒｎ杂交观察ＩＣＡＭ－１的蛋白和基因的表达，以电泳迁移率变动法测定转录因子核因子ｋＢ （ＮＦｋＢ）和激活蛋白 Ｉ（ＡＰ－１）的活性。结果ＴＮＦα呈剂量依赖地诱导ＨＫ－２细胞ＮＦｋＢ的活化及ＩＣＡＭ－１的基因和蛋白表达，这些作用可以被ＮＦｋＢ的抑制剂对甲苯磺－Ｌ－苯丙氨酸氯甲基甲酮（ＴＰＣＫ）所抑制，但ＴＮＦα对ＨＫ－２细胞的ＡＰ－１活性无影响。 ＩＬ－１０（１～ ２０ｎｇ／ｍｌ）可抑制 ＴＮＦα诱导的 ＨＫ－２细胞 ＩＣＡＭ－ｌ基因和蛋白表达及 ＮＦｋＢ的活化。结论ＴＮＦα诱导人肾小管上皮细胞ＨＫ－２的ＮＦｋＢ活化，进而促进ＩＣＡＭ－ｌ基因和蛋白表达，ＩＬ－１０可抑制ＴＮＦα诱导的上述炎症效应。Objecive To explore the effect of interleukin-10(IL10) on tumor necrosis factor-α(TNFα)- induced expression of intercellular adhesion molecule 1 (ICAM-1 )and related transcription pathway in human renal tubular cells. Methods Human renal proximal tubular cell line HK-2 cell was used as target cell. ICAM-1 was measured by cell ELISA and Northern blot in protein and mBNA levels. Activities of transcriptional factors nuclear factor GB(NFkB) and activator protein 1 (AP-1) were determined by electrophoresis mobility shift assay. Results TNFα-induced ICAM-l expression in HK-2 cells was increased in both protein and mNRA levels(P < 0.01 ). NFkB inhibitor N-tosyl phenyalanine chlormethyl ketone (TPCK)could inhibit these effects of TNLFα. TNFα had no effect on AP-l activity with doses of 1 ng/ml to 100 ng/ml and incubation periods of one to four hours. IL-10 iuhibited TNFα-induced ICALM-1 protein expression in dosage from 1 ng/ml to 20 ng/ml(decreased by 25 .7% to 35. 1 %, P < 0.05), as well as ICAM-1 mRNA expression and activity of NFkB in HK-2 cells. Conclusions TNFα induces ICAM-l expression in HK-2 cells through activation of NFkB. Inhibitory effect of IL-10 on ICAM-l expression induced by TNFα is mediated by, at least in a part, down-regulation of NFkB activity.

关 键 词：肾小管间质病变 白细胞介素10 ICAM-1 HK-2细胞 

分 类 号：R692.6[医药卫生—泌尿科学]