The KPV peptide (lysine‑proline‑valine) was shown in lab tests to protect skin cells from damage caused by fine dust particles. It cuts down harmful oxidative stress, blocks inflammation signals, and stops the cells from dying, working at about 50 µg/mL in cell cultures and a 3‑D skin model.

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 (PM₁₀) in human HaCaT keratinocytes. Our results show that PM₁₀ markedly 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 PM₁₀ exposure. To counteract PM₁₀-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 PM₁₀-treated HaCaT cells. Against PM₁₀-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 PM₁₀. Collectively, these findings suggest that KPV protects keratinocytes by mitigating PM₁₀-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.