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
MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP-70 signaling, and lymphocyte chemotaxis
Setareh Alampour-Rajabi,Omar El Bounkari,Antal Rot,Gerhard Müller-Newen,Françoise Bachelerie,Meinrad Gawaz,Christian Weber,Andreas Schober,Jürgen Bernhagen,Jürgen Bernhagen +9 more
TL;DR: B cells from Cxcr7‐/‐ mice exhibited an ablated transmigration response to MIF, indicating that CXCR7 is essential for MIF‐promoted B‐cell migration, and suggest a functional role of the M IF‐CX CR7 axis in B‐lymphocyte migration.
Journal ArticleDOI
The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer.
TL;DR: The roles of the CXCL12/CXCR4/C XCR7 axis in cancer progression and strategies to develop novel targeted cancer therapies are described and summarized.
Journal ArticleDOI
Genomics of Human Intracranial Aneurysm Wall
Changbin Shi,Issam A. Awad,Issam A. Awad,Nadereh Jafari,Simon Lin,Pan Du,Ziad A. Hage,Robert Shenkar,Robert Shenkar,Christopher C. Getch,Markus Bredel,H. Hunt Batjer,Bernard R. Bendok +12 more
TL;DR: The differentially expressed genes in the aneurysm wall may shed light on aneurYSm pathobiology and provide novel targets for therapeutic intervention and generate hypotheses for future studies.
Journal ArticleDOI
Atherosclerosis and the role of immune cells.
Fulya Ilhan,Sevgi Tas Kalkanli +1 more
TL;DR: Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes and T-cells produce pro-inflammatory mediators such as IFN-γ and upregulate macrophages to adhere to the endothelium and migrate into the intima.
Journal ArticleDOI
A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses
Daniela Kamir,Swen Zierow,Swen Zierow,Lin Leng,Yoonsang Cho,Yira Diaz,Jason W. Griffith,Courtney McDonald,Melanie Merk,Melanie Merk,Robert A. Mitchell,John O. Trent,Yibang Chen,Yuen-Kwan Amy Kwong,Huabao Xiong,Jon J. Vermeire,Michael Cappello,Diane McMahon-Pratt,John K. Walker,Jürgen Bernhagen,Elias Lolis,Richard Bucala +21 more
TL;DR: An ortholog of the cytokine, macrophage migration inhibitory factor, Lm1740MIF, which is produced by the obligate intracellular parasite, Leishmania major, shows significant structural homology with human MIF and inhibits the activation-induced apoptosis of macrophages.
References
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