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
More filters
Journal ArticleDOI
Macrophage migration inhibitory factor modulates formalin induced behaviors in rats
Alexandru Deftu,Paolo Fiorenzani,Ilaria Ceccarelli,Jessica Pinassi,Martina Gambaretto,Violeta Ristoiu,Luana Paulesu,A.M. Aloisi +7 more
TL;DR: Results suggest a possible effect of cytokine MIF on central nervous processes implicated in pain modulation mediated by the receptor CXCR2.
Dissertation
Investigations into the protective effects of the Multiple Myeloma Bone Marrow Microenvironment
TL;DR: Therapies targeting the PI3K isoforms or MIF (alongside conventional MM therapeutics) could therefore benefit MM patient treatment, and warrants clinical investigation.
Journal ArticleDOI
Kinetics of Parasite-Specific Antibody and B-Cell-Associated Gene Expression in Brown Trout, Salmo trutta during Proliferative Kidney Disease
TL;DR: In this article, the authors studied the anti-T. bryosalmonae antibody response in brown trout at different time points during chronic kidney disease (PKD) and found that T.bryosalminae specific antibody was detected at 4 weeks post exposure (wpe) and it persisted until 17 wpe, and the expression of C4A, CD34, CD79A, BLNK, CD74, BCL7, and CD22 were differentially regulated in the important immune organs, kidney and spleen.
Book ChapterDOI
Pathophysiology and Treatment of Pulmonary Arterial Hypertension
TL;DR: This chapter discusses the pathogenesis of PAH and the development of associated right heart failure, and provides an overview of currently approved medications and treatment options under investigation.
References
More filters
Journal ArticleDOI
Inflammation in atherosclerosis
TL;DR: The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
Journal ArticleDOI
Inflammation, Atherosclerosis, and Coronary Artery Disease
TL;DR: The evidence is recounted that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree.
Journal ArticleDOI
International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
William A. Catterall,K. G. Chandy,David E. Clapham,George A. Gutman,Franz Hofmann,Anthony J. Harmar,Darrell R. Abernethy,Michael Spedding +7 more
TL;DR: This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined.
Journal ArticleDOI
The Many Roles of Chemokines and Chemokine Receptors in Inflammation
TL;DR: The properties of chemokines and their receptors are discussed and the roles of these chemoattractants in selected clinical disorders are highlighted.
Book ChapterDOI
Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
TL;DR: In this paper, the authors focused on interleukin-8 (IL-8) and related chemotactic cytokines, namely, CXC and CC chemokines.