Journal ArticleDOI
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment
Jürgen Bernhagen,Regina M. Krohn,Hongqi Lue,Julia L. Gregory,Alma Zernecke,Rory R. Koenen,Manfred Dewor,Ivan T. Georgiev,Andreas Schober,Lin Leng,Teake Kooistra,Gunter Fingerle-Rowson,Pietro Ghezzi,Robert Kleemann,Shaun R. McColl,Richard Bucala,Michael J. Hickey,Christian Weber +17 more
TLDR
Targeting MIF in individuals with manifest atherosclerosis can potentially be used to treat this condition and displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.Abstract:
The cytokine macrophage migration inhibitory factor (MIF) plays a critical role in inflammatory diseases and atherogenesis. We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF. MIF triggered G αi- and integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin activation and calcium influx through CXCR2 or CXCR4. MIF competed with cognate ligands for CXCR4 and CXCR2 binding, and directly bound to CXCR2. CXCR2 and CD74 formed a receptor complex, and monocyte arrest elicited by MIF in inflamed or atherosclerotic arteries involved both CXCR2 and CD74. In vivo, Mif deficiency impaired monocyte adhesion to the arterial wall in atherosclerosis-prone mice, and MIF-induced leukocyte recruitment required Il8rb (which encodes Cxcr2). Blockade of Mif but not of canonical ligands of Cxcr2 or Cxcr4 in mice with advanced atherosclerosis led to plaque regression and reduced monocyte and T-cell content in plaques. By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis. Targeting MIF in individuals with manifest atherosclerosis can potentially be used to treat this condition. © 2007 Nature Publishing Group.read more
Citations
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Journal ArticleDOI
Ischemia and reperfusion related myocardial inflammation: A network of cells and mediators targeting the cardiomyocyte
TL;DR: The role of the cellular interplay in ischemia‐reperfusion injury from a cardiomyocyte‐centered view is discussed, although the author is aware that other cellular interactions are equally important.
Journal ArticleDOI
Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies
TL;DR: Macrophage migration inhibitory factor (MIF) as mentioned in this paper is a proinflammatory cytokine encoded within a functionally polymorphic genetic locus, which is a highly conserved 12.5 kDa secretory protein that is involved in numerous biological processes.
Journal ArticleDOI
Brain miffed by macrophage migration inhibitory factor
TL;DR: Acting as an endogenous glucocorticoid antagonist, MIF thus represents a relevant resistance gene in brain tumor therapies and the possibility of MIF targeting in neurodegenerative processes and brain tumors by novel MIF-neutralizing approaches is considered.
Journal ArticleDOI
Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies.
Krishnamoorthi Sumaiya,Dianne Langford,Kalimuthusamy Natarajaseenivasan,Kalimuthusamy Natarajaseenivasan,Santhanam Shanmughapriya +4 more
TL;DR: Macrophage migration inhibitory factor (MIF) as discussed by the authors is a proinflammatory cytokine encoded within a functionally polymorphic genetic locus and has been identified as a key cytokine secreted by many other cell types involved in immune response and physiological processes.
Journal ArticleDOI
Targeting chemokine pathways in esophageal adenocarcinoma
Makardhwaj Sarvadaman Shrivastava,Zulfiqar Hussain,Orsolya Giricz,Niraj Shenoy,Rahul Polineni,Anirban Maitra,Amit Verma +6 more
TL;DR: It is demonstrated that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation.
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