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
The Role of Macrophage Inhibitory Factor in Tumorigenesis and Central Nervous System Tumors
Jan-Philipp Bach,Oliver Deuster,Monika Balzer-Geldsetzer,Bernhard Meyer,Richard Dodel,Michael Bacher +5 more
TL;DR: The aim of this article was to present a detailed review of current knowledge regarding the role of MIF in CNS tumor pathophysiology.
Journal ArticleDOI
Thrombin and vascular inflammation
Milan Popovic,Katarina Smiljanic,Branislava Dobutovic,Tatiana Syrovets,Thomas Simmet,Esma R. Isenovic +5 more
TL;DR: This review summarizes the existing evidence on the role of thrombin in vascular inflammation and shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis.
Journal ArticleDOI
Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis.
Isabella Kanzler,Isabella Kanzler,Nancy Tuchscheerer,Guy C. M. Steffens,Sakine Simsekyilmaz,Simone Konschalla,Andreas Kroh,David Simons,Yaw Asare,Andreas Schober,Richard Bucala,Christian Weber,Christian Weber,Jürgen Bernhagen,Elisa A. Liehn +14 more
TL;DR: A role is identified for EPC-derived proangiogenic MIF, VEGF and MIF receptors in EPC recruitment following hypoxia, EPC differentiation and subsequent tube and vessel formation, whereas CXCL12, a mediator of early EPC recruited cells, does not contribute to the remodeling process.
Journal ArticleDOI
Expression profiles of cytokines in the brains of Alzheimer's disease (AD) patients compared to the brains of non-demented patients with and without increasing AD pathology.
Kaori Morimoto,Juri Horio,Haruhisa Satoh,Lucia I. Sue,Thomas G. Beach,Seizaburo Arita,Ikuo Tooyama,Yoshihiro Konishi +7 more
TL;DR: The results indicate that cytokines are more mobilized and implicated in the later AD stage when a significant cognitive decline occurs and develops than in the developmental course of AD pathology prior to the manifestation of overt dementia.
Journal ArticleDOI
The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis.
TL;DR: The current article focusses on MIF's role in vascular biology and pathology as recent evidence points to a role for this mediation in neo-angiogenesis / vasculogenesis by endothelial cell activation and endothelial progenitor cell recruitment.
References
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Journal ArticleDOI
The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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