Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway.

Airborne particulate matter (PM) poses a major environmental risk that impairs skin health by triggering oxidative stress, inflammation, and cell death. In this study, we investigated the protective effects of Lysine-Proline-Valine (KPV)-an endogenous peptide derived from α-melanocyte-stimulating hormone-against oxidative damage and inflammation induced by fine PM (PM) in human HaCaT keratinocytes. Our results show that PMmarkedly suppresses HaCaT cell proliferation via cytotoxic effects and induces a pro-inflammatory response by increasing IL-1β secretion. Notably, treatment with 50 μg/mL of KPV restored cell viability and reduced IL-1β secretion disrupted by PMexposure. To counteract PM-induced cell death, KPV inhibited reactive oxygen species (ROS) production, which is responsible for activating extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Additionally, KPV decreased the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and IL-1β through suppression of the redox-sensitive transcription factor nuclear, factor-kappa B in PM-treated HaCaT cells. Against PM-induced inflammation, KPV effectively blocked ROS-mediated caspase-1 activation, reducing IL-1β secretion. In a three-dimensional (3D) skin model, KPV treatment effectively attenuated the inflammatory cell death induced by PM. Collectively, these findings suggest that KPV protects keratinocytes by mitigating PM-induced pyroptosis and holds potential as a therapeutic agent for preventing environmental pollutant-related skin damage, with promising applications in functional cosmetics and skin-protective treatments.