title: Afadin requirement for cytokine expressions in keratinocytes during chemically induced inflammation in mice.
abstract: Afadin is a filamentous actin-binding protein and a mediator of nectin signaling. Nectins are Ig-like cell adhesion molecules, and the nectin family is composed of four members, nectin-1 to nectin-4. Nectins show homophilic and heterophilic interactions with other nectins or proteins on adjacent cells. Nectin signaling induces formation of cell-cell junctions and is required for the development of epithelial tissues, including skin. This study investigated the role of afadin in epithelial tissue development and established epithelium-specific afadin-deficient (CKO) mice. Although showing no obvious abnormality in the skin development and homeostasis, the mice showed the reduced neutrophil infiltration into the epidermis during chemical-induced inflammation with 12-O-tetradecanoylphorbol 13-acetate (TPA). 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. Primary-cultured skin keratinocytes from CKO mice also showed reduced expression of these cytokines and weak activation of Rap1 compared with those from control mice after the TPA treatment. These results suggested a remarkable function of afadin, which was able to enhance cytokine expression through Rap1 activation in keratinocytes during inflammation.
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takanori
authors.initials: T
authors.lastname: Iwata
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamato
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D061251:Primary Cell Culture; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; C108835:afadin; D020827:rap1 GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate