Dual effects of progesterone on HaCaT human keratinocytes: apoptosis induction and suppression of oxidative stress and TLR2 expression with potential implications for hyperplastic skin disorders

Objectives Hyperplastic skin disorders such as psoriasis are characterized by excessive keratinocyte proliferation, impaired apoptosis, oxidative stress, and sustained activation of innate immune pathways. While conventional treatment primarily targets these mechanisms, emerging interest focuses on the immunomodulatory roles of sex hormones such as progesterone (P4). Clinical observations that psoriasis symptoms often improve during pregnancy, when P4 levels increase, further support this hypothesis. However, the direct effects of P4 on keratinocyte behavior and related molecular pathways remain poorly understood. The study aimed to evaluate the impact of P4 on key pathological features of keratinocytes using the HaCaT cell line as an in vitro model. Methods HaCaT cells were cultured in DMEM medium with 10 % FBS and 1 % penicillin/streptomycin. Cells treated with various concentrations of P4, as well as untreated controls, were incubated at 37 °C incubator with 5 % CO 2 for 1–3 days. Following treatment, cell viability, apoptosis, oxidative stress, and Toll-like receptor 2 (TLR2) expression were assessed using MTT assay and flow cytometry. Results P4 significantly reduces keratinocyte proliferation and promotes apoptosis. Moreover, it also decreased intracellular reactive oxygen species (ROS) levels and downregulated TLR2 surface expression (p value≤0.05). Conclusions These findings highlight the multifaceted ability of P4 to modulate keratinocyte biology by regulating proliferation, apoptosis, oxidative balance, and inflammatory signaling. Interestingly, these effects occurred despite the absence of specific membrane P4 receptors, suggesting alternative pathways may mediate its actions. Further investigations under inflammatory conditions and in vivo models are warranted to validate these results and explore potential therapeutic applications.