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
Obacunone causes sustained expression of MKP-1 thus inactivating p38 MAPK to suppress pro-inflammatory mediators through intracellular MIF
TL;DR: It is concluded that OBA exerts its anti‐inflammatory effect by targeting intracellular MIF (inMIF) inhibition to regulate the MKP‐1/p38/AP‐1 pathway.
Journal ArticleDOI
CXCR4 and MIF are required for neutrophil extracellular trap release triggered by Plasmodium-infected erythrocytes
Danielle A. S. Rodrigues,Elisa Beatriz Prestes,Andreza Moreira Gama,Leandro S. Silva,Ana Acacia S. Pinheiro,José M. C. Ribeiro,Raquel Maria Pereira Campos,Pedro M. Pimentel-Coelho,Heitor S. de Souza,Alassane Dicko,Patrick E. Duffy,Michal Fried,Ivo M.B. Francischetti,Elvira M. Saraiva,Heitor A. Paula-Neto,Marcelo T. Bozza +15 more
TL;DR: It is shown that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma, indicating a role for NETs in resistance against Plasmodium infection.
Journal ArticleDOI
Toxoplasma gondii: Impaired maturation and pro-inflammatory response of dendritic cells in MIF-deficient mice favors susceptibility to infection
Cesar Terrazas,Imelda Juárez,Luis I. Terrazas,Rafael Saavedra,Elsa A. Calleja,Miriam Rodriguez-Sosa +5 more
TL;DR: It is demonstrated that MIF-induced early DC maturation and IL-12 production mediate resistance to T. gondii infection.
Journal ArticleDOI
Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.
Georgios Pantouris,Junming Ho,Junming Ho,Dilip Shah,Mansoor Ali Syed,Lin Leng,Vineet Bhandari,Vineet Bhandari,Richard Bucala,Victor S. Batista,J. Patrick Loria,Elias Lolis +11 more
TL;DR: Dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation are revealed.
Journal ArticleDOI
Gremlin-1 inhibits macrophage migration inhibitory factor-dependent monocyte function and survival
Iris Müller,Madhumita Chatterjee,Martina Schneider,Oliver Borst,Peter Seizer,Tanja Schönberger,Sebastian Vogel,Karin Müller,Tobias Geisler,Florian Lang,Harald F. Langer,Meinrad Gawaz +11 more
TL;DR: Gremlin-1 can modulate MIF dependent monocyte adhesion, migration, differentiation and survival and inhibit the anti-apoptotic impact of MIF on monocytes against BH3 mimetic ABT-737-induced apoptosis.
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.