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

Summary

This in vitro study tested whether Lysine-Proline-Valine (KPV), an endogenous tripeptide derived from α-melanocyte-stimulating hormone, protects human HaCaT keratinocytes against damage from fine airborne particulate matter (PM10). PM10 exposure cut cell proliferation and raised the pro-inflammatory cytokine IL-1β, while KPV at 50 µg/mL restored viability and lowered IL-1β. Mechanistic work showed KPV suppresses ROS production, dampening ERK/p38 MAPK and NF-κB signaling and reducing apoptosis- and pyroptosis-related markers. The protective effect was confirmed in a three-dimensional skin model.

Key Findings

• Fine particulate matter (PM10) suppressed HaCaT keratinocyte proliferation via cytotoxicity and drove a pro-inflammatory response by increasing IL-1β secretion.
• Treatment with 50 µg/mL KPV restored cell viability and reduced the IL-1β secretion disrupted by PM10 exposure.
• KPV inhibited reactive oxygen species (ROS) production, which is responsible for activating ERK and p38 MAPK.
• KPV decreased apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) and IL-1β through suppression of the redox-sensitive transcription factor NF-κB.
• KPV blocked ROS-mediated caspase-1 activation to reduce IL-1β, and in a 3D skin model attenuated the inflammatory cell death induced by PM10.

Relevance to KPV

This work extends the anti-inflammatory profile of KPV beyond the gut into the skin, showing that the α-MSH-derived tripeptide can shield keratinocytes from a real-world environmental stressor. The reported mechanism — ROS quenching upstream of MAPK and NF-κB, with downstream suppression of both apoptosis and caspase-1-driven pyroptosis — is consistent with KPV’s known role as an anti-inflammatory melanocortin fragment, and it echoes the melanocortin lineage KPV shares with agents such as Melanotan-II. As an in vitro and 3D-skin-model study, the findings are preclinical and point toward topical or cosmetic use rather than established clinical benefit.

Citation

Sung J, Ju SY, Park S, et al. Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway. Tissue & cell. 2025. doi:10.1016/j.tice.2025.102837.

See Also

• Parent compound: KPV