CADMIUM-INDUCED RENAL DAMAGE AND PROINFLAMMATORY CYTOKINES - POSSIBLE ROLE OF IL-6 IN TUBULAR EPITHELIAL-CELL REGENERATION
CADMIUM-INDUCED RENAL DAMAGE AND PROINFLAMMATORY CYTOKINES - POSSIBLE ROLE OF IL-6 IN TUBULAR EPITHELIAL-CELL REGENERATION
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DOI：
10.1006/taap.1995.1165
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发表时间：
1995-09-01
影响因子：
3.8
通讯作者：
LUSTER, MI
中科院分区：
文献类型：
--
作者：
KAYAMA, F;YOSHIDA, T;LUSTER, MI
在人类和实验动物中，镉暴露会导致肾损害，其特征是肾小管上皮细胞变性和坏死，随后是间质炎症，并最终导致近端肾小管细胞再生。由于慢性肾脏疾病通常与炎性细胞因子的存在有关，而且镉已被报道改变单核细胞和肝脏Kupffer细胞中细胞因子的表达，我们研究了促炎细胞因子在镉诱导的肾毒性中的作用，观察到脂多糖诱导的小鼠在14周内总共摄入21 mg/kg镉后，肾脏中肿瘤坏死因子-α和IL-6细胞因子的mRNA转录和分泌增加。IL-6是主要的细胞因子，存在于系膜细胞中。在体外，镉可诱导小鼠肾小球系膜细胞分泌IL-6。增殖细胞核抗原(PCNA)染色显示，镉暴露后肾小管上皮细胞再生增加。此外，肾小管上皮细胞对IL-6有明显的增殖反应。综上所述，这些数据表明，镉诱导的肾脏IL-6分泌可能对镉肾毒性过程中发生的肾小管上皮细胞再生起支持作用。(C)1995年学术出版社。
Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity, Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity. (C) 1995 Academic Press, Inc.