INTERLEUKIN-1-ALPHA AND TUMOR NECROSIS FACTOR-ALPHA INDUCE OXYGEN RADICAL PRODUCTION IN MESANGIAL CELLS
INTERLEUKIN-1-ALPHA AND TUMOR NECROSIS FACTOR-ALPHA INDUCE OXYGEN RADICAL PRODUCTION IN MESANGIAL CELLS
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DOI：
10.1038/ki.1990.44
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发表时间：
1990-02-01
影响因子：
19.6
通讯作者：
RESCH, K
中科院分区：
文献类型：
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作者：
RADEKE, HH;MEIER, B;RESCH, K
贴壁的人肾小球系膜细胞（HMC）不能吞噬血清处理的酵母聚糖（STZ），然而，这种刺激（1 mg/ml）诱导H2 O2和O2-释放以3.15 ± 1.5mg/ml的速率显著立即增加。0.35和3.40 .+-。0.12 nmol/106 HMC/hr。单独的酵母多糖不导致H2 O2或O2-的释放。佛波醇肉豆蔻酸酯乙酸酯（PMA，2 × 100）10-6 M）对HMC仅具有边际效应，导致产生0.273 . 0.014 nmol O2-/106 HMC/hr。（TNF-α）和人重组白细胞介素1-α。（IL-1 α。两者都诱导了显著的O2-产生，以细胞色素c的SOD可逆还原来测量，5 × 10 - 6。10-5 M，粘附HMC达5小时，最大速率为3.04 ±。0.08和3.2 .+-。0.08 nmol/106 HMC/hr，对于IL-1 α。和TNF-α，分别在0.625 ng/ml（37 pM）IL-1 α下可检测到显著的O2释放。或1 ng/ml（59 pM）TNF-α。（P < 0.05）。过氧化氢酶可降解的H2 O2的产生也由IL-1 α诱导。和TNF-α以剂量依赖的方式。使用东莨菪亭（40 nM）和1 μ M过氧化物酶，我们用荧光法测量1.73 ± 0.01。0.14和1.49 . ±. 0.19 IL-1 α诱导的nmol H2 O2/106 HMC/hr。(25 ng/ml）和TNF-α。(20 ng/ml）。最后，我们确定了自由基的类型HMC细胞因子刺激采用ESR自旋捕获DMPO。这些结果表明，O2-是形成的主要自由基物种。因此，我们首次证实HMC能够响应IL-1 α而产生显著的氧自由基。和TNF-α，其量与单核细胞产生的量相当。这些结果可能与人类肾小球肾炎的发病机制有关。
Adherent human mesangial cells (HMC) were unable to phagocytose serum-treated zymosan (STZ), nevertheless this stimulus (1 mg/ml) induced a marked immediate increase of H2O2 and O2- release at a rate of 3.15 .+-. 0.35 and 3.40 .+-. 0.12 nmol/106 HMC/hr, respectively. Zymosan alone resulted in no release of either H2O2 or O2-. Phorbol myristate acetate (PMA, 2 .times. 10-6 M) had only marginal effects on HMC leading to the generation of 0.273 .+-. 0.014 nmol O2-/106 HMC/hr. After a lag period, human recombinant tumor necrosis factor-.alpha. (TNF-.alpha.) and human recombinant interleukin 1-.alpha. (IL-1.alpha. both induced significant O2- production measured as SOD inhibitable reduction of cytochrome c, 5 .times. 10-5 M, by adherent HMC for up to five hours, the maximum rates being 3.04 .+-. 0.08 and 3.2 .+-. 0.08 nmol/106 HMC/hr for IL-1.alpha. and TNF-.alpha., respectively. Significant O2- release was detectable at 0.625 ng/ml (37 pM) IL-1.alpha. or 1 ng/ml (59 pM) TNF-.alpha. (P < 0.05). Catalase inhibitable H2O2 production was also induced by IL-1.alpha. and TNF-.alpha. in a dose dependent manner. Using scopoletin (40 nM) and 1 .mu.M peroxidase we fluorimetrically measured 1.73 .+-. 0.14 and 1.49 .+-. 0.19 nmol H2O2/106 HMC/hr induced by IL-1.alpha. (25 ng/ml) and TNF-.alpha. (20 ng/ml). Finally, we ascertained the type of radical species produced by HMC stimulated by cytokines employing ESR-spin-trapping with DMPO. These results demonstrated that O2- was the primary radical species formed. We have thus established for the first time that HMC are able to generate significant oxygen radicals in response to IL-1.alpha. and TNF-.alpha., in amounts comparable to that produced by monocytes. These findings may be relevant to the pathogenesis of human glomerulonephritis.