Macrophage migration inhibitory factor: a regulator of innate immunity.
Macrophage migration inhibitory factor: a regulator of innate immunity.
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DOI：
10.1038/nri1200
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发表时间：
2003-10
期刊：
影响因子：
--
通讯作者：
Roger T
中科院分区：
文献类型：
--
作者：
Calandra T;Roger T
细胞因子是先天免疫的基本效应分子，其启动和协调细胞和体液应答，例如，旨在根除微生物病原体。细胞因子巨噬细胞移动抑制因子（MIF）在20世纪60年代末作为活化的T细胞的产物被发现，最近已经发现作为先天免疫系统的介体执行重要功能。MIF由包括单核细胞和巨噬细胞在内的广谱细胞和组织组成性表达，在暴露于微生物产物和促炎介质后以及响应于应激而快速释放。释放后，MIF诱导促炎生物反应，作为免疫反应的调节剂。MIF激活细胞外信号调节激酶1（ERK 1）/ERK 2-促分裂原活化蛋白激酶途径，抑制JUN活化结构域结合蛋白1（JAB 1）-活化蛋白1（AP 1）的共活化剂-的活性，上调Toll样受体4的表达以促进表达内毒素的细菌病原体的识别，通过抑制巨噬细胞的p53依赖性凋亡维持促炎功能，并反调节糖皮质激素对免疫细胞的免疫抑制作用。作为一种促炎介质，MIF已被证明与严重脓毒症和脓毒性休克、急性呼吸窘迫综合征以及包括类风湿性关节炎、肾小球肾炎和炎性肠病在内的几种其他炎性和自身免疫性疾病的发病机制有关。鉴于其作为先天性和获得性免疫调节剂的关键作用，MIF活性的药理学或免疫学调节可能为急性和慢性炎症性疾病的管理提供新的治疗机会。世纪以来，巨噬细胞移动抑制因子（MIF）一直是一种神秘的细胞因子。近年来，MIF作为先天免疫的关键调节因子发挥了重要作用。MIF是宿主抗菌警报系统和应激反应的组成部分，促进免疫细胞的促炎功能。近年来，越来越多的文献表明MIF参与了脓毒症、炎症性疾病和自身免疫性疾病的发病机制，提示以MIF为靶点的治疗可能为人类疾病的治疗提供新的机会。
Cytokines are essential effector molecules of innate immunity that initiate and coordinate the cellular and humoral responses aimed, for example, at the eradication of microbial pathogens. Discovered in the late 1960s as a product of activated T cells, the cytokine macrophage migration inhibitory factor (MIF) has been discovered recently to carry out important functions as a mediator of the innate immune system. Constitutively expressed by a broad spectrum of cells and tissues, including monocytes and macrophages, MIF is rapidly released after exposure to microbial products and pro-inflammatory mediators, and in response to stress. After it is released, MIF induces pro-inflammatory biological responses that act as a regulator of immune responses. MIF activates the extracellular signal-regulated kinase 1 (ERK1)/ERK2–mitogen-activated protein kinase pathway, inhibits the activity of JUN activation domain-binding protein 1 (JAB1) — a co-activator of the activator protein 1 (AP1) — upregulates the expression of Toll-like receptor 4 to promote the recognition of endotoxin-expressing bacterial pathogens, sustains pro-inflammatory function by inhibiting p53-dependent apoptosis of macrophages and counter-regulates the immunosuppressive effects of glucocorticoids on immune cells. As a pro-inflammatory mediator, MIF has been shown to be implicated in the pathogenesis of severe sepsis and septic shock, acute respiratory distress syndrome, and several other inflammatory and autoimmune diseases, including rheumatoid arthritis, glomerulonephritis and inflammatory bowel diseases. Given its crucial role as a regulator of innate and acquired immunity, pharmacological or immunological modulation of MIF activity might offer new treatment opportunities for the management of acute and chronic inflammatory diseases. For more than a quarter of a century, macrophage migration inhibitory factor (MIF) has been a mysterious cytokine. In recent years, MIF has assumed an important role as a pivotal regulator of innate immunity. MIF is an integral component of the host antimicrobial alarm system and stress response that promotes the pro-inflammatory functions of immune cells. A rapidly increasing amount of literature indicates that MIF is implicated in the pathogenesis of sepsis, and inflammatory and autoimmune diseases, suggesting that MIF-directed therapies might offer new treatment opportunities for human diseases in the future.
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