Rat hepatocytes and Kupffer cells interact to produce interleukin-8 (CINC) in the setting of ethanol.
Rat hepatocytes and Kupffer cells interact to produce interleukin-8 (CINC) in the setting of ethanol.
复制标题
在乙醇环境中，大鼠肝细胞和 Kupffer 细胞相互作用产生白细胞介素 8 (CINC)。
DOI：
10.1152/ajpgi.1995.269.4.g518
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Maher,JJ
中科院分区：
文献类型：
--
作者：
Maher,JJ
白细胞介素-8是一种中性粒细胞趋化剂，与酒精性肝炎的发病机制有关。虽然肝细胞和库普弗细胞都被认为是趋化因子的来源，但乙醇诱导肝脏产生白细胞介素-8的机制尚不确定。在这项研究中，我们研究了短期乙醇暴露是否会刺激正常大鼠肝细胞和原代培养的Kupffer细胞产生大鼠白细胞介素-8（细胞因子诱导的中性粒细胞化学引诱物（CINC））。初步实验证实肝细胞和库普弗细胞在细胞因子或脂多糖的作用下产生CINC。相比之下，即使浓度高达100 mM，乙醇也不能刺激两种细胞类型的CINC分泌。尽管乙醇对肝细胞CINC的产生没有直接影响，但乙醇处理肝细胞的条件培养基诱导库普弗细胞CINC的产生增加了三倍。当肝细胞用乙醇和代谢抑制剂4-甲基吡唑处理时，这种增加被消除。结果表明，乙醇诱导CINC产生的机制是间接的，涉及乙醇氧化和肝细胞与Kupffer细胞之间的通讯。
Interleukin-8 is a neutrophil chemoattractant that has been implicated in the pathogenesis of alcoholic hepatitis. The mechanism of ethanol-induced interleukin-8 production in liver is uncertain, although hepatocytes and Kupffer cells have both been proposed as sources of the chemokine. In this study we investigated whether short-term ethanol exposure stimulates production of rat interleukin-8 [cytokine-induced neutrophil chemoattractant (CINC)] by normal rat hepatocytes and Kupffer cells in primary culture. Initial experiments verified that hepatocytes and Kupffer cells produce CINC in response to cytokines or lipopolysaccharide. Ethanol, by contrast, failed to stimulate CINC secretion by either cell type even at concentrations as high as 100 mM. Although ethanol had no direct effect on liver cell CINC production, conditioned medium from ethanol-treated hepatocytes induced a threefold rise in CINC production by Kupffer cells. The increase was abrogated when hepatocytes were treated with ethanol and the metabolic inhibitor 4-methylpyrazole. The results suggest that the mechanism of ethanol-induced CINC production is indirect, involving ethanol oxidation and communication between hepatocytes and Kupffer cells.