Mechanical and Metabolic Injury to the Skin Barrier Leads to Increased Expression of Murine β-Defensin-1, -3, and -14

Protection of the skin against microbiological infection is provided by the permeability barrier and by antimicrobial proteins. We asked whether the expression of murine beta-defensins (mBDs)-1, -3, and -14-orthologs of human beta-defensins hBD-1, -2, and -3, respectively-is stimulated by mechanically/physicochemically (tape stripping or acetone treatment) or metabolically (essential fatty acid-deficient (EFAD) diet) induced skin barrier dysfunction. Both methods led to a moderate induction of mBD-1 and mBD-14 and a pronounced induction of mBD-3 mRNA. Protein expression of the mBDs was increased as shown by immunohistology and by western blotting. Artificial barrier repair by occlusion significantly reduced the increased expression of mBD-14 after mechanical injury and of all three mBDs in EFAD mice, supporting an interrelationship between permeability and the antimicrobial barrier. mBD-3 expression was stimulated in vitro by tumor necrosis factor-alpha (TNF-alpha), and a neutralizing anti-TNF-alpha antibody significantly reduced increased mBD-3 expression after barrier injury in mouse skin, indicating that induction of mBD-3 expression is mediated by cytokines. The expression of mBD-14 was stimulated by transforming growth factor-alpha and not by TNF-alpha. In summary, we demonstrated upregulation of mBD1, -3, and -14 after mechanically and metabolically induced skin barrier disruption, which may be an attempt to increase defense in the case of permeability barrier dysfunction.