title: Involvement of MIF in basement membrane damage in chronically UVB-exposed skin in mice.
abstract: Solar ultraviolet (UV) B radiation is known to induce matrix metalloproteinases (MMPs) that degrade collagen in the basement membrane. Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in the pathophysiology of skin inflammation induced by UV irradiation. This study examined the effects of MIF on basement membrane damage following chronic UVB irradiation in mice. The back skin of MIF transgenic (Tg) and wild-type (WT) mice was exposed to UVB three times a week for 10 weeks. There was a decrease in intact protein levels of type IV collagen and increased basement membrane damage in the exposed skin of the MIF Tg mice compared to that observed in the WT mice. Moreover, the skin of the MIF Tg mice exhibited higher MIF, MMP-2 and MMP-9 expression and protein levels than those observed in the WT mice. We also found that chronic UVB exposure in MIF Tg mice resulted in higher levels of neutrophil infiltration in the dermis compared with that observed in the WT mice. In vitro experiments revealed that MIF induced increases in the MMPs expression, including that of MMP-9 in keratinocytes and MMP-2 in fibroblasts. Cultured neutrophils also secreted MMP-9 stimulated by MIF. Therefore, MIF-mediated basement membrane damage occurs primarily through MMPs activation and neutrophil influx in murine skin following chronic UVB irradiation.
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihisa
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Norisugi
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Department of Medical Information, Hokkaido Information University, Ebetsu, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000528:radiation effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression / Q000528:radiation effects; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D007555:Isoxazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000201:enzymology; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D015533:Transcriptional Activation / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse