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
Inhibition of WHSC1 Allows for Reprogramming of the Immune Compartment in Prostate Cancer.
TL;DR: In this article, a single-cell analysis of the intratumoral immune dynamics following in vivo pharmacological inhibition of WHSC1 in mice grafted with TRAMP C2 cells was performed.
Journal ArticleDOI
Assessment of macrophage migration inhibitory factor in patients with verruca vulgaris.
TL;DR: The significantly elevated MIF levels in lesional and perilesional skin biopsies compared to controls point to its role in wart progression from HPV infected cells.
Journal ArticleDOI
Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo
Christine Meyer,Jesse Dewane,Kristen Haberthur,Flora Engelmann,Nicole Arnold,Wayne L. Gray,Ilhem Messaoudi +6 more
TL;DR: SVV BAC is as pathogenic and immunogenic as WT SVV in vivo and can further the understanding of viral ORFs important for VZV pathogenesis and the development of second-generation vaccines.
Journal ArticleDOI
Suppression of Plasmodium MIF-CD74 signaling protects against severe malaria.
Alvaro Baeza Garcia,Edwin Siu,Xin Du,Lin Leng,Blandine Franke-Fayard,Chris J. Janse,Shanshan W. Howland,Laurent Rénia,Elias Lolis,Richard Bucala +9 more
TL;DR: In this article, the authors investigated the PMIF-CD74 interaction in the onset of experimental cerebral malaria (ECM) and liver stage Plasmodium development by using a combination of CD74 deficient (Cd74-/- ) hosts and PMIF deficient parasites.
Journal ArticleDOI
Characteristics of Waldenström Macroglobulinemia in Korean Patients According to Mutational Status of MYD88 and CXCR4: Analysis Using Ultra-Deep Sequencing.
Dong Woo Shin,Sung Min Kim,Jung Ah Kim,Hee Sue Park,Sang Mee Hwang,Sang Mee Hwang,Kyongok Im,Sungsik Kim,Jinhyun Kim,Sunghoon Kwon,Sung-Soo Yoon,Dong Soon Lee +11 more
TL;DR: The frequency of MYD88/CXCR4 muts in Korean and Caucasian patients with WM was similar, however 5 of the 6 CXCR 4 muts were nonsense-a proportion higher than reported frequencies in Caucasian individuals.
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.