Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes
Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes
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DOI：
10.1016/s0008-6363(01)00408-4
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发表时间：
2001-12-01
影响因子：
10.8
通讯作者：
Shimada, K
中科院分区：
文献类型：
--
作者：
Takahashi, M;Nishihira, J;Shimada, K
目的：巨噬细胞迁移抑制因子（MIF）在控制炎症反应中发挥着关键作用，最初被定性为T细胞细胞因子，但后来也被发现是响应感染和应激而释放的垂体肽。然而，MIF在心肌中的作用和表达尚未见报道。本研究的目的是检查心肌中的 MIF。方法和结果：分别使用酶联免疫吸附测定（ELISA）和逆转录聚合酶链反应（RT-PCR）测定MIF蛋白和mRNA水平。在急性心肌梗塞 (AMI) 患者的血清中检测到 MIF 浓度升高。在培养的大鼠心肌细胞中，缺氧和过氧化氢 (H2O2) 会产生大量 MIF，但血管紧张素 II、内皮素 I、白细胞介素 1β (IL-1β) 或肿瘤坏死因子 α (TNFα) 不会产生显着量的 MIF。 H2O2 诱导的 MIF 产生以时间和剂量依赖性方式增加，但在过氧化氢酶存在下完全消除。 H2O2 还诱导 MIF mRNA 表达。 H2O2 诱导的 MIF 产生被蛋白激酶 C (PKC) 抑制剂 GF109203X 完全抑制，被酪氨酸激酶抑制剂除草霉素 A 部分抑制，并且不受钙螯合或佛波酯敏感 PKC 下调的抑制。这表明 H2O2 诱导的 MIF 产生是由非典型 PKC 同工型介导的。 DNA 微阵列分析显示，52 个基因响应 MIF 优先表达。其中。 RT-PCR 分析证实了 MIF 诱导的谷胱甘肽 S-转移酶 (GST) 和脂多糖诱导的 CXC 趋化因子 (LIX) mRNA 的表达。结论：目前的结果表明，MIF 是心肌响应氧化还原应激而表达的，可能在心肌缺血的发病机制中发挥作用。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Objective: Macrophage migration inhibitory Factor (MIF), which plays a pivotal role in the control of inflammatory responses was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium has never been reported. The goal of this study is to examine MIF in the myocardium. Methods and results: MIF protein and mRNA levels were assayed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Increased MIF concentrations were detected in the sera of patients with acute myocardial infarction (AMI). In cultured rat cardiac myocytes, significant amounts of MIF were produced in response to hypoxia and hydrogen peroxide (H2O2), but not to angiotensin II, endotliclin-I, interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha). H2O2-induced MIF production increased in a time- and dose-dependent manner and was completely abolished in the presence of catalase. H2O2 also induced MIF mRNA expression. The H2O2-induced MIF production was completely inhibited by the protein kinase C (PKC) inhibitor GF109203X, partially inhibited by the tyrosine kinase inhibitor herbimycin A, and uninhibited by calcium chelation or phorbol ester-sensitive PKC down-regulation. This suggests that H2O2-induced MIF production is mediated by an atypical PKC isoform. DNA microarray analysis revealed that 52 genes were preferentially expressed in response to MIF. Of these. the MIF-induced expression of both glutathione S-transferase (GST) and lipopolysaccharide-induced CXC chemokine (LIX) mRNA, was confirmed using RT-PCR analysis. Conclusion: The present results suggest that MIF is expressed by the myvocardium in response to redox stress and may play a role in the pathogenesis of myocardial ischemia. (C) 2001 Elsevier Science B.V. All rights reserved.