title: The antimicrobial peptide pheromone Plantaricin A increases antioxidant defenses of human keratinocytes and modulates the expression of filaggrin, involucrin, β-defensin 2 and tumor necrosis factor-α genes.
abstract: 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.
authors: Giuliani S.p.A. R&D, Milan, Italy.
authors: Barbara
authors: B
authors: Marzani
authors: Daniela
authors: D
authors: Pinto
authors: Fabio
authors: F
authors: Minervini
authors: Maria
authors: M
authors: Calasso
authors: Raffaella
authors: R
authors: Di Cagno
authors: Giammaria
authors: G
authors: Giuliani
authors: Marco
authors: M
authors: Gobbetti
authors: Maria
authors: M
authors: De Angelis
mesh_terms: D000704:Analysis of Variance; D001430:Bacteriocins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D024502:alpha-Tocopherol / Q000494:pharmacology; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D001430:Bacteriocins; C106641:DEFB4A protein, human; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008070:Lipopolysaccharides; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C084446:plantaricin A; C032253:involucrin; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; D024502:alpha-Tocopherol