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
Editorial: The CXCR4 Ligand/Receptor Family and the DPP4 Protease in High-Risk Cardiovascular Patients
Heidi Noels,Jürgen Bernhagen +1 more
TL;DR: The reader is introduced to the comorbidities T2DM and CKD and their connection with CVD, and up-to-date information on the involvement of CXCL12/MIF/CXCR4 and DPP4 in each of these pathologies is provided.
Inflammation and its echo in atherosclerosis
TL;DR: The role of inflammation in the pathophysiology of atherosclerosis is examined from different angles and the effect of various pro-inflammatory mediators is examined in the context of atherogenesis.
Journal ArticleDOI
Development of Mimokines, chemokine N terminus-based CXCR4 inhibitors optimized by phage display and rational design.
Virginie Fievez,Martyna Szpakowska,Amor Mosbah,Karthik Arumugam,Julie Mathu,Manuel Counson,Nadia Beaupain,Carole Seguin-Devaux,Sabrina Deroo,Michèle Baudy-Floc’h,Andy Chevigné +10 more
TL;DR: Optimized Mimokines, which imitate the chemokine‐binding mode but display an enhanced receptor affinity, antiviral properties, and receptor selectivity, are identified and may therefore serve as lead compounds for further development of more selective CXCR4 peptide inhibitors and probes.
Journal ArticleDOI
Molecular mechanisms regulating metastasis of cancer cells with special emphasis on rhabdomyosarcoma
Maciej Tarnowski,Katarzyna Grymula,Marta Tkacz,Michał Czerewaty,Agata Poniewierska-Baran,Mariusz Z. Ratajczak +5 more
TL;DR: The processes and mechanisms described herein, such as chemotaxis, adhesion, proliferation, intracellular signal transduction, seem to universal for number of cancer types.
References
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