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
Novel anti-inflammatory strategies in atherosclerosis.
TL;DR: An overview of promising anti-inflammatory therapies in atherosclerosis is provided, and novel imaging modalities such as MRI and PET-computed tomography provide valuable surrogate inflammatory endpoints for risk stratification and testing anti- inflammatory agents in cardiovascular randomized trials.
Journal ArticleDOI
Down-regulation of MIF by NFκB under hypoxia accelerated neuronal loss during stroke
Si Zhang,Odysseus Zis,Philip T. T. Ly,Yili Wu,Shuting Zhang,Mingming Zhang,Fang Cai,Richard Bucala,Woei Cherng Shyu,Weihong Song +9 more
TL;DR: It is shown that MIF expression is down‐regulated by 0.75 ± 0.10‐fold and that down‐regulation of MIF by NFκB‐mediated signaling under hypoxia accelerates neuronal loss during stroke.
Journal ArticleDOI
Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase
Nicola N. Lynskey,Mark Reglinski,Damien Calay,Matthew K. Siggins,Justin C Mason,Marina Botto,Shiranee Sriskandan +6 more
TL;DR: Data show that ScpA is a multi-functional virulence factor with both complement-dependent and independent roles in streptococcal pathogenesis, and identifies C3 and C3a as novel substrates for the strePTococcal ScPA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase.
Journal ArticleDOI
Up-regulation of vascular endothelial growth factor-D expression in clear cell renal cell carcinoma by CD74: a critical role in cancer cell tumorigenesis.
TL;DR: Evidence is provided that the intracellular signaling cascade responsible for VEGF-D up-regulation by CD74 is both PI3K/AKT- and MEK/ERK-dependent, both of which are associated with NF-κB nuclear translocation and DNA-binding activity.
Journal ArticleDOI
The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma
Lin Zhang,Shu Biao Ye,Gang Ma,Xiao Feng Tang,Shi Ping Chen,Jia He,Wan Li Liu,Dan Xie,Yi Xin Zeng,Jiang Li +9 more
TL;DR: The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC.
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.