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首页> 外文期刊>World Journal of Gastroenterology >Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells
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Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells

机译:来氟米特通过抑制库普弗细胞减轻肝细胞损伤

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摘要

AIM: To investigate the importance of direct contact between Kupffer cells (KCs) and hepatocytes (HCs) during hepatic inflammatory responses, and the effect of leflunomide's active metabolite, A_(771726), on cytokines in KCs, HCs and KC cocultures (DC cocultures). METHODS: KCs and HCs in liver were isolated by digestion with pronase and collagenase. Lipopolysaccharide (LPS)-induced inflammatory response in monocultures of rat HCs and KCs was compared with that in DC cocultures. Tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) concentrations in different culture supernatants were measured with ELISA. TNF-α mRNA in KCs of inflammatory liver injury was analyzed with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: DC cocultures strongly exhibited the production of TNF-α and IL-1 compared with other cultures, and these cytokines were mainly produced by KCs, especially by activated KCs. Time course studies revealed an increased production of TNF-α preceding the IL-1 production, suggesting that increased TNF-α levels could be involved in the increase of IL-1 production. Leflunomide's active metabolite, A_(771726), had significantly inhibitory effect on TNF-α and IL-1 at protein and transcription levels, and the reduced production of IL-1 by A_(771726) was associated with the inhibitory action of A_(771726) on TNF-α. CONCLUSION: Leflunomide can inhibit hepatocyte damage by inhibiting proinflammatory cytokine release from KCs.
机译:目的:研究肝炎性反应期间库普弗细胞(KCs)和肝细胞(HCs)之间直接接触的重要性,以及来氟米特的活性代谢产物A_(771726)对KCs,HCs和KC共培养物(DC共培养物)细胞因子的影响)。方法:用链霉蛋白酶和胶原酶消化分离肝脏中的KCs和HCs。将脂多糖(LPS)诱导的大鼠HCs和KCs单一培养物中的炎症反应与DC共培养物中的炎症反应进行了比较。用ELISA测定不同培养上清液中的肿瘤坏死因子-α(TNF-α)和白介素-1(IL-1)的浓度。用逆转录聚合酶链反应(RT-PCR)分析炎性肝损伤KCs中的TNF-αmRNA。结果:DC共培养物比其他培养物强烈显示TNF-α和IL-1的产生,并且这些细胞因子主要由KC产生,特别是由活化的KC产生。时程研究显示,IL-1产生之前TNF-α的产生增加,这表明TNF-α水平升高可能与IL-1产生的增加有关。来氟米特的活性代谢产物A_(771726)在蛋白质和转录水平上对TNF-α和IL-1有明显的抑制作用,并且A_(771726)降低IL-1的产生与A_(771726)的抑制作用有关)在TNF-α上。结论:来氟米特可通过抑制KCs释放促炎细胞因子来抑制肝细胞损伤。

著录项

  • 来源
    《World Journal of Gastroenterology》 |2004年第11期|p.1608-1611|共4页
  • 作者单位

    Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, School of Medicine, Zhejiang University, Hangzhou 310031, Zhejiang Province, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
  • 关键词

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