Macrophage migration inhibitory factor.
Macrophage migration inhibitory factor (MIF) is a ubiquitous protein that is found in virtually all cells. Its precise function in the majority of cells is not known, but studies performed over the last decade indicate that it is a critical upstream regulator of the innate and acquired immune response. MIF is released under a variety of circumstances, regulates cytokine secretion and the expression of receptors that are involved in innate immunity, inhibits p53 function, and activates components of the mitogen-activated protein kinase and Jun-activation domain-binding protein-1 (Jab-1) pathways. Compelling in vitro and in vivo evidence has focused attention on this protein as a new therapeutic target for inflammatory and autoimmune diseases. Unique structural features, including an intrinsic catalytic activity, offer attractive opportunities for the discovery and design of therapeutic MIF inhibitors.
Lolis
Elias
E
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. elias.lolis@yale.edu
Bucala
Richard
R
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000503:physiopathology; D000075686:COP9 Signalosome Complex; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D005938:Glucocorticoids / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007239:Infections / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism; D010447:Peptide Hydrolases / Q000502:physiology; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology
D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D008263:Macrophage Migration-Inhibitory Factors; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D020782:Matrix Metalloproteinases