Macrophage inhibitory factor

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Function

Macrophage inhibitory factor or Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine. MIF2 or D-dopachrome tautomerase or D-dopachrome decarboxylase is a pro-inflammatory cytokine which regulates the innate and adaptive immune response[1]. MIF is released to the blood stream upon stimulation of white blood cells by bacterial antigens[2].

Relevance

MIF plays a role in various solid and hematologic tumors[3]. MIF is overexpressed in various tumors and is suggested to be the molecular link between chronic inflammation and cancer. MIF has a role in skin inflammation, immune response, disease, tumorigenesis and wound healing[4]. MIF has a role in Alzheimer disease and its inhibition may prevent the disease onset[5].

Structural highlights

MIF contains two different catalytic sites. A phenylpyruvate tautomerase site is located in the N terminal. A . The [6]. Water molecules shown as red spheres.

3D structures of macrophage inhibitory factor

Macrophage inhibitory factor 3D structures


Structure of human macrophage inhibitory factor trimer complex with inhibitor, glycerol and sulfate (PDB entry 2ooh)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Merk M, Mitchell RA, Endres S, Bucala R. D-dopachrome tautomerase (D-DT or MIF-2): doubling the MIF cytokine family. Cytokine. 2012 Jul;59(1):10-7. doi: 10.1016/j.cyto.2012.03.014. Epub 2012 Apr 14. PMID:22507380 doi:http://dx.doi.org/10.1016/j.cyto.2012.03.014
  2. ↑ Nishihira J. Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth. J Interferon Cytokine Res. 2000 Sep;20(9):751-62. PMID:11032394 doi:http://dx.doi.org/10.1089/10799900050151012
  3. ↑ Bach JP, Deuster O, Balzer-Geldsetzer M, Meyer B, Dodel R, Bacher M. The role of macrophage inhibitory factor in tumorigenesis and central nervous system tumors. Cancer. 2009 May 15;115(10):2031-40. doi: 10.1002/cncr.24245. PMID:19326434 doi:http://dx.doi.org/10.1002/cncr.24245
  4. ↑ Shimizu T. Role of macrophage migration inhibitory factor (MIF) in the skin. J Dermatol Sci. 2005 Feb;37(2):65-73. PMID:15659324 doi:http://dx.doi.org/10.1016/j.jdermsci.2004.08.007
  5. ↑ Bacher M, Deuster O, Aljabari B, Egensperger R, Neff F, Jessen F, Popp J, Noelker C, Reese JP, Al-Abed Y, Dodel R. The role of macrophage migration inhibitory factor in Alzheimer's disease. Mol Med. 2010 Mar;16(3-4):116-21. doi: 10.2119/molmed.2009.00123. Epub 2010 Feb, 28. PMID:20200619 doi:http://dx.doi.org/10.2119/molmed.2009.00123
  6. ↑ Crichlow GV, Cheng KF, Dabideen D, Ochani M, Aljabari B, Pavlov VA, Miller EJ, Lolis E, Al-Abed Y. Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor. J Biol Chem. 2007 Aug 10;282(32):23089-95. Epub 2007 May 25. PMID:17526494 doi:http://dx.doi.org/10.1074/jbc.M701825200

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