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
MIF Promotes Classical Activation and Conversion of Inflammatory Ly6C(high) Monocytes into TipDCs during Murine Toxoplasmosis.
Juan de Dios Ruiz-Rosado,Jonadab E. Olguín,Imelda Juárez-Avelar,Rafael Saavedra,Luis I. Terrazas,Frank Robledo-Avila,Alicia Vazquez-Mendoza,Jacquelina Fernández,Abhay R. Satoskar,Santiago Partida-Sanchez,Miriam Rodriguez-Sosa +10 more
TL;DR: An important role for MIF inducing cell-mediated immunity to T. gondii infection is found and it is found that MIF promotes maturation of CD11b+ but not CD8α + DCs, by inducing IL-12p70 production and CD86 expression.
Journal ArticleDOI
Open Sesame! CXCR4 Blockade Recruits Neutrophils Into the Plaque
Julie Sainz,Masataka Sata +1 more
TL;DR: Neutrophil infiltrates are seldom observed within human atherosclerotic plaques in comparison with other inflammatory cells, and the increase in proinflammatory molecules occurring with coronary artery diseases correlates with the peripheral neutrophil count, which may be useful as a predictor of complex coronary stenosis or myocardial infarction.
Journal ArticleDOI
Experimental immunotherapeutic approaches for atherosclerosis.
TL;DR: There is now accumulating data in animal models demonstrating the potential for immunotherapeutic approaches to treat atherosclerosis, and these include both general and antigen-specific ways of modulating immune functions, and they show great promise for the development of alternative and/or adjuvant therapies for Atherosclerosis.
Journal ArticleDOI
A selective small-molecule inhibitor of macrophage migration inhibitory factor-2 (MIF-2), a MIF cytokine superfamily member, inhibits MIF-2 biological activity.
Pathricia V. Tilstam,Georgios Pantouris,Michael Corman,Monica Andreoli,Keyvan Mahboubi,Gary Davis,Xin Du,Lin Leng,Elias Lolis,Richard Bucala +9 more
TL;DR: An in silico screen of 1.6 million compounds targeting the MIF-2 tautomerase site yielded several hits for potential catalytic inhibitors of Mif-2 and identified 4-(3-carboxyphenyl)-2,5-pyridinedicarboxylic acid (4-CPPC) as the most functionally potent compound.
Journal ArticleDOI
Pharmacological opportunities to control inflammatory diseases through inhibition of the leukocyte recruitment.
TL;DR: Mechanisms of leukocyte recruitment are reviewed and potential targets for the development of novel anti-inflammatory therapies are suggested.
References
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Journal ArticleDOI
The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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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.