Afadin requirement for cytokine expressions in keratinocytes during chemically induced inflammation in mice.
Bottom Line: Nectin signaling induces formation of cell-cell junctions and is required for the development of epithelial tissues, including skin.Immunohistochemical and quantitative real-time PCR analyses showed that the expression levels of cytokines including Cxcl2, Il-1β and Tnf-α were reduced in CKO keratinocytes compared with control keratinocytes during TPA-induced inflammation.These results suggested a remarkable function of afadin, which was able to enhance cytokine expression through Rap1 activation in keratinocytes during inflammation.
Affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo, 162-8666, Japan.Show MeSH
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Mentions: The adult mouse back was denuded, and 12-O-tetradecanoylphorbol 13-acetate (TPA) was applied onto the back skin once a day for 3 days (Fig.3A, E). The TPA treatment induced skin inflammation and the infiltration of inflammatory cells into the epidermis (intra-epidermal microabscess, IEM) in the skin (Fig.3B, C, D). In CKO mice, the cell infiltrated area was smaller than that of control skin after TPA treatment (Fig.3F–I). Immunohistochemistry showed that the cells in IEMs were mostly neutrophils (Gr-1 positive) and that there were few T cells (CD3 positive) (Fig.4A, B). IEMs in CKO skin showed severely reduced neutrophil infiltration (Fig.4D, E). Although an obvious abnormality in the formation of IEMs was observed in CKO skin, the expression and localization of skin differentiation markers and junctional proteins were comparable to those in control skin (Fig.4C, F–L).
Affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo, 162-8666, Japan.