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
Porphyromonas gingivalis-Induced MIF Regulates Intercellular Adhesion Molecule-1 Expression in EA.hy926 Cells and Monocyte-Endothelial Cell Adhesion Through the Receptors CD74 and CXCR4.
Yun Wu,Wanyue Xu,Jingya Hou,Yanqing Liu,Rong Li,Jingbo Liu,Chen Li,Xiaolin Tang,Li Lin,Yaping Pan,Dongmei Zhang +10 more
TL;DR: By interacting with the CD74/CXCR4 receptor complex, MIF may act as a crucial regulator of monocyte-endothelial cell adhesion and promote the atherosclerotic plaque formation induced by P. gingivalis.
Journal ArticleDOI
Role of Host and Parasite MIF Cytokines during Leishmania Infection.
Thomas Holowka,Richard Bucala +1 more
TL;DR: The immune response to Leishmania in mouse models and humans will be reviewed, and the properties and activities of mammalian and Leishmaniasis MIF will be integrated into the current understandings in this field.
Journal ArticleDOI
Macrophage-mediated response to hypoxia in disease
TL;DR: Evidence for hypoxia-driven macrophage inflammatory responses in various disease states is reviewed, and how this influences disease progression and treatment is reviewed.
Journal ArticleDOI
Macrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells
Lisa Schindler,Lisa Schindler,Leon Zwissler,Christine Krammer,Ulrike B. Hendgen-Cotta,Tienush Rassaf,Mark B. Hampton,Nina Dickerhof,Jürgen Bernhagen +8 more
TL;DR: In this paper, it was shown that both MIF and MIF-2/D-DT inhibit neutrophil apoptosis, and that blocking the interaction between the two factors could be an important anti-inflammatory strategy in the early inflammatory response.
Journal ArticleDOI
Macrophage migration inhibitory factor enhances Pseudomonas aeruginosa biofilm formation, potentially contributing to cystic fibrosis pathogenesis.
Aisling Tynan,Leona Mawhinney,Michelle E. Armstrong,Ciaran O’Reilly,Sarah Kennedy,E. Caraher,Karen Jülicher,David N O'Dwyer,Lewena Maher,Kirsten Schaffer,Aurelie Fabre,Edward F. McKone,Lin Leng,Richard Bucala,Jürgen Bernhagen,Gordon Cooke,Seamas C. Donnelly +16 more
TL;DR: In vivo studies demonstrate that utilizing a small‐molecular‐weight inhibitor targeting MIF’s tautomerase activity significantly reduces the inflammatory response in a murine pulmonary chronic P. aeruginosa model and support the concept of an anti‐MIF strategy that targets this enzymatic activity as a potential future antibacterial therapeutic approach.
References
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The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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