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
Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells
Nina Baron,Oliver Deuster,Carmen Noelker,Carsten Stüer,Herwig Strik,Carlo Schaller,Richard Dodel,Bernhard Meyer,Michael Bacher +8 more
TL;DR: Inhibition of MIF with ISO‐1, an inhibitor of the D‐dopachrome tautomerase site of Mif, reduced the growth rate of primary GBM cells in a dose‐dependent manner, and in additionISO‐1 increased protein expression of M IF and its receptors CD74, CX CR2, and CXCR4 in vitro but decreased expression of CD44.
Journal ArticleDOI
Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation
Mie Torii,Linan Wang,Ning Ma,Kanako Saito,Tomohide Hori,Tomohide Hori,Maremi Sato-Ueshima,Yoshikazu Koyama,Hiroyoshi Nishikawa,Naoyuki Katayama,Akira Mizoguchi,Hiroshi Shiku,Junji Yodoi,Kagemasa Kuribayashi,Takuma Kato +14 more
TL;DR: It is shown here that IL‐13 and eotaxin production are decreased in TRX‐Tg mice leading to reduced eosinophils recruitment and mucus metaplasia, and production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX'ed mice.
Journal ArticleDOI
There Is Always Another Way! Cytomegalovirus’ Multifaceted Dissemination Schemes
Joseph W. Jackson,Tim E. Sparer +1 more
TL;DR: The historic and recent literature pointing to CMV’s direct dissemination to secondary organs and the genes that it has evolved for increasing its ability to disseminate are reviewed.
Journal ArticleDOI
Reduced Osteoarthritis Severity in Aged Mice With Deletion of Macrophage Migration Inhibitory Factor.
Meredith A. Rowe,Lindsey Harper,Margaret A. McNulty,Anthony G. Lau,Cathy S. Carlson,Lin Leng,Richard Bucala,Richard A. Miller,Richard F. Loeser +8 more
TL;DR: The potential role of MIF in osteoarthritis in human joint tissues and in vivo in mice with age-related and surgically induced OA was investigated in this article.
Journal ArticleDOI
Tumor-derived macrophage migration inhibitory factor promotes an autocrine loop that enhances renal cell carcinoma.
Weinan Du,Bradley M. Wright,Xin Li,James H. Finke,Brian I. Rini,Ming Zhou,H He,Priti Lal,Scott M. Welford +8 more
TL;DR: MIF is established as a protumorigenic signaling molecule that functions in an autocrine fashion to promote renal cell carcinoma and may be useful as a minimally invasive marker of disease status in CCRC.
References
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