Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule.
The immunological and neuroendocrine properties of macrophage migration inhibitory factor (MIF) are diverse. In this article we review the known cellular, molecular and genetic properties of MIF that place it as a key regulatory cytokine, acting within both the innate and adaptive immune responses. The unexpected and paradoxical induction of MIF secretion by low concentrations of glucocorticoids is explored. The role of MIF as a locally acting modulator of glucocorticoid sensitivity within foci of inflammation is also discussed. MIF has no homology with any other pro-inflammatory cytokine and until recently lacked a recognised transmembrane receptor. MIF has also been shown to be directly taken up into target cells and to interact with intracellular signalling molecules, including the Jun activation domain-binding protein Jab-1.Comprehensive analysis of the MIF gene has identified important functional polymorphisms and a series of genetic studies has revealed both association and linkage of MIF with inflammatory diseases. Altered MIF regulation may therefore be pivotal to acquiring chronic inflammation following an innate immune response.
Donn
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Arthritis Research Campaign/Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. Rachell@fs1.ser.man.ac.uk
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D000818:Animals; D000075686:COP9 Signalosome Complex; D004268:DNA-Binding Proteins / Q000378:metabolism; D008040:Genetic Linkage; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007109:Immunity / Q000502:physiology*; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D010447:Peptide Hydrolases; D011110:Polymorphism, Genetic; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; D008263:Macrophage Migration-Inhibitory Factors; D014157:Transcription Factors; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex