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.

Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

“…Plantaricin A, a bacteriocin produced by Lactobacillus plantarum, has been shown to increase cell proliferation, enhance migration, and influence the expression of transforming growth factor ␤1, fibroblast growth factor 7, vascular endothelial growth factor A, and interleukin-8 in vitro in human keratinocytes (60). Plantaricin A was shown to promote antioxidant defenses and increased the expression of FLG, IVL and HBD-2 genes in NCTC 2544 keratinocytes (61). Decreased expression of tumor necrosis factor alpha was also observed in plantaricin A-treated cells.…”

Therapeutics and Other Interventions

“…These studies need to be replicated. The candidates include sericin-rich diets (animal study) [ 35 ]; apigenin, an active constituent in chrysanthemum (in vitro study) [ 36 ]; interferon-γ (in vitro study) [ 21 ]; hyaluronic acid; and bacterial antimicrobial peptide plantaricin A (in vitro study) [ 37 ]. Urea, a well-known humectant, also possesses fi laggrin upregulatory effects and may prove more versatile than previously assumed [ 38 ].…”

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

“…Production of reactive oxygen species (ROS) was monitored spectrofluorometrically using the 2 0 ,7 0 -dichlorofluorescein diacetate (DCFH-DA) method, as previously described [12,21]. Normal human NCTC 2544 keratinocytes (HL97002) (Istituto Nazionale di Ricerca sul Cancro, Genoa, Italy) were treated with vehicle, N 1 -MeSpd or a-tocopherol, the principal form of vitamin E, used as a positive control as a known potent antioxidant [6].…”

“…1), to assess its functional effects on HFs, using microdissected, organ-cultured human scalp HFs as a physiologically and clinically relevant assay system [18]. The effects of N 1 -MeSpd were further dissected in a human keratinocyte cell line (NCTC 2544) [12].…”