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
AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice
Daria Barwinska,Houssam Oueini,Christophe Poirier,Marjorie Albrecht,Natalia V. Bogatcheva,Matthew J. Justice,Matthew J. Justice,Jacob Saliba,Kelly S. Schweitzer,Kelly S. Schweitzer,Hal E. Broxmeyer,Keith L. March,Irina Petrache +12 more
TL;DR: Results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.
Journal ArticleDOI
Murine Glucocorticoid Receptors Orchestrate B Cell Migration Selectively between Bone Marrow and Blood.
Derek W. Cain,Carl D. Bortner,David Díaz-Jiménez,Maria Grazia Petrillo,Amanda Gruver-Yates,John A. Cidlowski +5 more
TL;DR: It is proposed that endogenous glucocorticoids regulate a dynamic mode of B cell migration specialized for rapid exchange between bone marrow and blood, perhaps as a means to optimize humoral immunity during diurnal periods of activity.
Journal ArticleDOI
Novel Role of Macrophage Migration Inhibitory Factor in Upstream Control of the Unfolded Protein Response After Ethanol Feeding in Mice
Kyle L. Poulsen,Megan R. McMullen,Emily Huang,Christopher D. Kibler,Megan M. Sheehan,Lin Leng,Richard Bucala,Laura E. Nagy +7 more
TL;DR: It is revealed that, in addition to its cytokine/chemokine functions, MIF is an upstream regulator of UPR in response to EtOH feeding in mice, which can either protect or contribute to liver injury, dependent upon the stage or severity of EtOH-induced liver injury.
Journal ArticleDOI
Macrophage migration inhibitory factor down-regulates the RANKL-RANK signaling pathway by activating Lyn tyrosine kinase in mouse models.
TL;DR: Whether MIF modulates osteoclastogenesis through Lyn phosphorylation, and whether down‐regulation of RANKL‐mediated signaling requires the association of CD74, CD44, and Lyn is examined.
Journal ArticleDOI
Intraluminal blockade of cell-surface CD74 and glucose regulated protein 78 prevents substance P-induced bladder inflammatory changes in the rat.
TL;DR: GRP78 is expressed on the surface of urothelial cells after substance P treatment where it can bind MIF complexes and blocking CD74 (receptor for MIF) and/or GRP78 prevented substance P-induced inflammatory changes in bladder and Urothelium, indicating that these urothalial receptors are effective targets for disrupting MIF-mediated bladder inflammation.
References
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