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
Macrophages and chemokines as mediators of angiogenesis.
TL;DR: This review summarizes the current literature regarding the roles and modes of action of macrophage-derived chemokines as mediators of angiogenesis and identifies several members of the CXC and CC chemokine families that are potent inducers of angoattractants.
Journal ArticleDOI
Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge.
Sven Brandau,Mark Jakob,Mark Jakob,Hatim Hemeda,Kirsten Bruderek,Sandra Janeschik,Friedrich Bootz,Stephan Lang +7 more
TL;DR: A complex, functional interaction between tissue‐resident MSCs and peripheral blood neutrophils upon bacterial challenge is demonstrated and a role for MSC's in the early phases of pathogen challenge, when classical immune cells have not been recruited yet is suggested.
Journal ArticleDOI
CXCR2-mediated tumor-associated neutrophil recruitment is regulated by IFN-β.
TL;DR: It is shown that the migration of neutrophils is influenced by endogenous interferon‐beta (IFN‐β) via regulation of such chemokines and their receptor, which adds a novel functional aspect of the type I IFN system as effector molecules of natural cancer surveillance and open interesting possibilities for antineutrophil therapies against cancer.
Journal ArticleDOI
Proinflammatory Signature of the Dysfunctional Endothelium in Pulmonary Hypertension. Role of the Macrophage Migration Inhibitory Factor/CD74 Complex
Morane Le Hiress,Ly Tu,Nicolas Ricard,Carole Phan,Raphaël Thuillet,Elie Fadel,Peter Dorfmüller,David Montani,David Montani,Frances S. de Man,Marc Humbert,Marc Humbert,Alice Huertas,Alice Huertas,Christophe Guignabert +14 more
TL;DR: It is reported here that CD74 and MIF are markedly increased and activated in patients with iPAH, contributing to the abnormal proinflammatory phenotype of pulmonary ECs in iPAh.
Journal ArticleDOI
Macrophage Migration Inhibitory Factor Contributes to the Immune Escape of Ovarian Cancer by Down-Regulating NKG2D
Mathias Krockenberger,Yvonne Dombrowski,Claudia Weidler,Monika Ossadnik,Arnd Honig,Sebastian Häusler,Heike Voigt,Jürgen C. Becker,Lin Leng,Alexander Steinle,Michael Weller,Richard Bucala,Johannes Dietl,Jörg Wischhusen +13 more
TL;DR: It is found that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells.
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.