The antimicrobial peptide pheromone Plantaricin A increases antioxidant defenses of human keratinocytes and modulates the expression of filaggrin, involucrin, beta-defensin 2 and tumor necrosis factor-alpha genes
Di Cagno R
De Angelis M
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Plantaricin A (PlnA) is a peptide with antimicrobial and pheromone activities. PlnA was synthesized chemically and used as a pure peptide or synthesized biologically using Lactobacillus plantarum DC400 co‐cultured with Lactobacillus sanfranciscensis DPPMA174. Cell‐free supernatant (CFS) was used as a crude PlnA preparation. As estimated using the 3‐(4,5‐dimethyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide and the 2’,7’–dichlorofluorescein diacetate assays, both PlnA preparations increased the antioxidant defenses of human NCTC 2544 keratinocytes. PlnA (10 μg/ml) had a higher activity than hyaluronic acid or 125 μg/ml α‐tocopherol. Effects on the transcriptional regulation of filaggrin (FLG), involucrin (IVL), hyaluronan synthase (HAS2), human β‐defensin‐2 (HBD‐2) and tumor necrosis factor‐alpha (TNF‐α) genes were assayed. Compared with the control, expression of the FLG gene in NCTC 2544 cells increased in cells treated with hyaluronic acid, 1 or 10 μg/ml PlnA. Compared with the control, the level of IVL gene expression increased in NCTC 2544 cells treated with 10 μg/ml PlnA. No significant difference was found between the level of the HAS2 gene expressed by control cells and cells treated with PlnA. Compared with chemically synthesized PlnA, the up‐regulation of the HBD‐2 gene by CFS was higher. Compared with the control, expression of TNF‐α decreased in NCTC 2544 cells after treatment with 1 or 10 μg/ml of chemically synthesized PlnA. In contrast, the level of TNF‐α was highest in the presence of 10 μg/ml CFS‐PlnA. These findings suggest that the PlnA was positively sensed by human keratinocytes, promoting antioxidant defenses, barrier functions and antimicrobial activity of the skin.