OBJECTIVE: Pediocin, a class IIa bacteriocin produced by Pediococcus species, exhibits potent antimicrobial activity primarily against Gram-positive bacteria. However, recent evidence suggests that some bacteriocins can also interact with eukaryotic cells, influencing host responses such as angiogenesis and wound repair. This study aimed to investigate the biological effects of pediocin on human gingival fibroblast (HGF) cells, focusing on its impact on angiogenesis- and wound healing–related pathways.MATERIAL AND METHODS: Human gingival fibroblast cells were treated with increasing concentrations of pediocin (10–200 nM). The gene expression levels of Vascular endothelial growth factor A (VEGFA), Epidermal growth factor (EGF), and Epidermal growth factor receptor (EGFR) were analyzed using quantitative real-time PCR to assess angiogenic and epithelial growth responses. A wound scratch assay was performed to evaluate the effects of pediocin on wound closure at different doses.RESULTS: Pediocin significantly increased VEGFA gene expression in a dose-dependent manner, with a 27.809-fold increase at 100 nM (p < 0.05), indicating its potential to promote angiogenesis. However, wound closure was negatively affected at higher concentrations: the control group achieved 85.3% wound closure at 24 hours, whereas treatment with 100 nM and 200 nM pediocin resulted in reduced wound closure (73.6% and 68.7%, respectively), representing approximately 14% and 19% impairment compared to control. Additionally, a 2.648-fold increase in EGF expression was observed at 100 nM (p < 0.0001), implying that pediocin modulates EGF signaling in a concentration-dependent manner. No significant changes were detected in EGFR expression (p > 0.05), suggesting indirect regulation of this pathway.CONCLUSIONS: Although VEGFA and EGF are crucial mediators of tissue repair, the complex and dose-dependent interactions of pediocin with these molecules highlight the need for further research into its therapeutic potential. Pediocin demonstrates both beneficial and detrimental effects, underscoring the importance of optimizing its dosage and timing for effective application in wound healing and possibly cancer therapy. These findings support the concept that bacteriocins act as dual-function molecules both antimicrobial and host-modulatory agents warranting continued investigation into their biological safety and therapeutic uses.

Herpes simplex virus Type 1 (HSV‐1) is a prevalent infectious agent globally, often causing oral infections like gingivostomatitis. The ICP0 protein of HSV‐1 exacerbates infection severity by inhibiting antiviral responses. Our study explored how combinations of CAPE (caffeic acid phenethyl ester) and acyclovir influenced immune responses in gingival cells treated with ICP0 We applied ICP0 protein, CAPE, acyclovir, and their combinations to HGF‐1 cells for 24 h. IC ₅₀ dose amounts were determined using the MTT cell viability test, gene expressions were assessed by RT‐PCR, and protein levels were gauged by the ELISA method. No statistically significant changes were noted between the ICP0 applied groups and the control groups ( p > 0.05). However, significant increases were observed in the IFN‐β ( p < 0.0001), IFN‐γ ( p < 0.0001), IRF3 ( p < 0.0001), β‐catenin ( p < 0.0001), WNT‐1 ( p < 0.0001). protein levels of the ICP0 + CAPE applied groups. The increases in all groups administered ICP0 + acyclovir surpassed those administered ICP0 + CAPE ( p < 0.0001). The combination of CAPE and acyclovir could potentially reduce both the adverse effects caused by the ICP0 protein and the undesirable side effects that may be caused by the acyclovir used in the treatment. This combination could serve as a potential therapy in the treatment of HSV‐1.

Rotavirus represents a predominant etiological agent of acute gastroenteritis among neonates and young pediatric populations. Rotavirus predominantly targets enterocytes, leading to diarrhea as a consequence of intestinal cellular impairment induced by the rotavirus nonstructural protein 4 (Nsp4) and subsequent stimulation of the enteric nervous system. Nsp4 serves as the principal protein accountable for the alterations in calcium (Ca²⁺) homeostasis within cells infected by rotavirus. This study investigated the effects of plantaricin A (PlnA), a Lactobacillus plantarum bacteriocin, on intracellular and extracellular Ca²⁺ and anti-inflammatory and proinflammatory cytokine levels in the Caco-2 intestinal cell line treated with the Nsp4 protein, which causes diarrhea and damage to enterocytes through various mechanisms in rotavirus infections. Nsp4 increased intracellular and extracellular Ca²⁺ levels over time, and PlnA suppressed this effect when applied with Nsp4. Consequently, PlnA has the capacity to diminish cytosolic Ca²⁺, a critical element utilized by the virus for replication during the initial phases of infection. PlnA increased the gene expression and protein levels of proinflammatory cytokines. In a comparable manner, PlnA elevated the transcriptional activity and protein concentrations of the anti-inflammatory cytokine IL-10, indicating that PlnA may exert an anti-inflammatory influence. If supported by in vivo studies, PlnA could be a therapeutic agent for treating viral enteritis.