Macrophage migration inhibitory factor regulates interleukin-6 production by facilitating nuclear factor-kappa B activation during Vibrio vulnificus infection.
Macrophage migration inhibitory factor regulates interleukin-6 production by facilitating nuclear factor-kappa B activation during Vibrio vulnificus infection.
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DOI：
10.1186/1471-2172-11-50
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发表时间：
2010-10-12
期刊：
影响因子：
3
通讯作者：
Lin CF
中科院分区：
文献类型：
--
作者：
Chuang CC;Chuang YC;Chang WT;Chen CC;Hor LI;Huang AM;Choi PC;Wang CY;Tseng PC;Lin CF
感染创伤弧菌（V. vulnificus）的患者表现出严重的炎症反应，其特征在于促炎细胞因子的上调。巨噬细胞移动抑制因子（MIF）是一种上游促炎调节因子，可增加脓毒症引起的炎症反应。MIF是否调节对创伤弧菌感染的反应以及创伤弧菌启动这些MIF调节的促炎细胞因子的实际机制仍不清楚。在体内创伤弧菌感染期间，MIF增加炎症。在创伤弧菌感染的小鼠中，MIF的产生早于肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6，并以时间依赖性方式表达。ISO-1（（S，R）-3-（4-hydroxyphenyl）-4，5-dihydro-5-isoxazole acetic acid methyl ester）是一种MIF的小分子抑制剂，可显著降低创伤弧菌感染的人外周血细胞中IL-6、IL-8和TNF-α的产生，并呈时间和剂量依赖性。创伤弧菌感染诱导IL-6、IL-8和TNF-α的产生是通过NF-κB和p38 MAPK调节的途径介导的，但不通过Akt途径介导。ISO-1处理的人外周血细胞显示出较低的创伤弧菌诱导的NF-κB活化、IL-6 mRNA表达和IκB磷酸化，但它们没有显示出较低的p38 MAPK活化。我们的结论是，MIF通过NF-κB激活调节创伤弧菌诱导的IL-6产生，创伤弧菌感染中p38 MAPK的激活不是MIF依赖性的。
Patients infected with Vibrio vulnificus (V. vulnificus) show severe inflammatory responses characterised by the upregulation of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), an upstream proinflammatory regulator, increases the inflammation caused by sepsis. Whether MIF regulates responses to V. vulnificus infection and the actual mechanism by which V. vulnificus initiates these MIF-modulated proinflammatory cytokines remain unclear. MIF increased inflammation during V. vulnificus infection in vivo. In V. vulnificus-infected mice, MIF was produced earlier than tumour necrosis factor (TNF)-α and interleukin (IL)-6 and was expressed in a time-dependent manner. ISO-1 ((S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester), a small-molecule inhibitor of MIF, significantly decreased IL-6, IL-8, and TNF-α production in a time- and dose-dependent manner in human peripheral blood cells infected with V. vulnificus. The induction of IL-6, IL-8, and TNF-α production by V. vulnificus infection was mediated via the NF-κB- and p38 MAPK-regulated pathways but not via the Akt pathway. ISO-1-treated human peripheral blood cells showed lower V. vulnificus-induced NF-κB activation, IL-6 mRNA expression, and IκB phosphorylation, but they did not show lower p38 MAPK activation. We conclude that MIF regulates V. vulnificus-induced IL-6 production via NF-κB activation and that p38 MAPK activation in V. vulnificus infection is not MIF dependent.
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