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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Patent
Methods of treating inflammatory disorders
TL;DR: In this paper, the authors present methods and compositions for treating inflammatory disorders. In some embodiments, the methods comprise co-administering synergistic combinations of modulators of inflammation, and in other embodiments, they combine modulators separately.
Journal ArticleDOI
Modulation of circulating macrophage migration inhibitory factor in the elderly.
Christos Rammos,Ulrike B. Hendgen-Cotta,Julia Pohl,Matthias Totzeck,Peter Luedike,Volker Schulze,Malte Kelm,Tienush Rassaf +7 more
TL;DR: The data show that supplementation with dietary nitrate is associated with a reduction of circulating MIF levels along with an improvement in vascular function, which supports the concept of dietary approaches to modulate age-related changes of vascular functions.
Journal ArticleDOI
Macrophage migration inhibitory factor increases cell motility and up-regulates αvβ3 integrin in human chondrosarcoma cells.
Chun-Yi Lee,Mei-Ju Su,Chun-Yin Huang,Meng-Yi Chen,Horng-Chaung Hsu,Ching-Yuang Lin,Chih-Hsin Tang +6 more
TL;DR: Results indicate that MIF enhanced the migration of the chondrosarcoma cells by increasing αvβ3 integrin expression through the PI3K/Akt/NF‐κB signal transduction pathway.
Journal ArticleDOI
Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-κB signaling pathway
Lin Zheng,Jiawei Gao,Kangtao Jin,Zhenzhong Chen,Weiyang Yu,Zhu Kejun,Huang Wenjun,Feijun Liu,Liangwei Mei,Chao Lou,Dengwei He +10 more
TL;DR: Evidence is provided for the pharmacological targeting of MIF for the treatment of osteolytic bone disorders by 4‐IPP, an irreversible inhibitor of macrophage migration inhibitory factor, which suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF‐κB signaling pathway.
Journal ArticleDOI
Small-molecule antagonist of macrophage migration inhibitory factor enhances migratory response of mesenchymal stem cells to bronchial epithelial cells
Bonnie L. Barrilleaux,Donald G. Phinney,Benjamin W. Fischer-Valuck,Katie C. Russell,Guoshun Wang,Darwin J. Prockop,Kim C. O'Connor +6 more
TL;DR: The data suggest that MIF and its antagonists may have therapeutic applications in controlling MSC homing during repair of injured lung and in other clinically relevant systems.
References
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The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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