title: Macrophage migration inhibitory factor is essential for eosinophil recruitment in allergen-induced skin inflammation.
abstract: Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that has an essential role in the pathophysiology of experimental allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including atopic dermatitis (AD). In this study, the role of MIF in allergic skin inflammation was examined using a murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA). We observed the number of skin-infiltrating eosinophils to significantly increase in OVA-sensitized MIF transgenic (Tg) mice compared with their wild-type (WT) littermates. On the other hand, eosinophils were virtually absent from the skin of MIF knockout (KO) mice and failed to infiltrate their skin after repeated epicutaneous sensitization with OVA. The mRNA expression levels of eotaxin and IL-5 were significantly increased in OVA-sensitized skin sites of MIF Tg mice, but were significantly decreased in MIF KO mice in comparison with the levels in WT littermates. Eotaxin expression was induced by IL-4 stimulation in fibroblasts in MIF Tg mice, but not in MIF KO mice. These findings indicate that MIF can induce eosinophil accumulation in the skin. Therefore, the targeted inhibition of MIF might be a promising new therapeutic strategy for allergic skin diseases.
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihisa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Makino
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Ayumi
authors.initials: A
authors.lastname: Honda
authors.forename: Osamu
authors.initials: O
authors.lastname: Norisugi
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology*; D020405:Dermis / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D015848:Interleukin-5; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D010047:Ovalbumin; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse