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

Abstract

Protection of the skin against microbiological infection is provided by the permeability barrier and by antimicrobial proteins. We asked whether the expression of murine β-defensins (mBDs)-1, -3, and -14-orthologs of human β-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-α (TNF-α), and a neutralizing anti-TNF-α 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-α and not by TNF-α. 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.

Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

“…Such concepts are consistent with recent studies of innate memory (51)(52)(53)(54)(55)(56). For example, dermal M⌽ are known to play key roles in innate memory (54).…”

“…Immunological determinants associated with the host defense against MRSA were assessed in skin abscesses at the study endpoint as we previously described (49,50,52). In brief, samples were aseptically dissected from animals, fixed in 10% zinc formalin, and embedded in paraffin.…”

Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus

“…After 7 days of infection, immunological determinants associated with host defense against MRSA were assessed in skin abscesses and kidneys (36). In brief, samples were aseptically dissected from animals, fixed in 10% zinc formalin, and embedded in paraffin.…”

Induction of Regulatory T Cells by a Murine β-Defensin

“…Skin samples collected from unirradiated mice were used as controls. Next, 5-mm-thick sections were deparaffinized and stained with a specific affinity-purified polyclonal goat anti-mBD-14 Ab, as described previously (15). Negative control staining was performed by omitting the primary Ab.…”