Involvement of MIF in Basement Membrane Damage in Chronically UVB-Exposed Skin in Mice
Authors
Yoko Yoshihisa, Osamu Norisugi, Kenji Matsunaga, Jun Nishihira, Tadamichi Shimizu
Institution
Uni Toyama
Country
Japan
Year
2014
Journal
PLOS
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.