LB1120 Naturally occurring phenolic compounds protect human keratinocytes against diesel exhaust particle-induced cell damage

Mammalian epidermis positioned at the interface with the environment, protecting underlying tissues from external challenges such as pollutants. Diesel exhaust particles (DEPs) are a major contaminator of air pollution particles, and emerging evidences indicate that polycyclic aromatic hydrocarbons (PAHs), a main component of DEPs, cause skin irritation and inflammation through aryl hydrocarbon receptor (AhR)-dependent signaling pathways. In particular, prior studies revealed that an AhR activation induces apoptotic-cell death via an increased level of cellular ceramide, an apoptotic molecule. In addition, we previously demonstrated that metabolic conversion of ceramide into sphingosine-1-phosphate (S1P) protects keratinocyte against ceramide-induced apoptosis. Therefore, we here investigated whether certain naturally-occurring compounds reduce air pollution particles-induced cell damage. First, we determined whether structurally- and functionally-different natural compounds could reduce DEPs-mediated increase in cellular apoptosis. Among fifteen naturally-occurring compounds tested, Euphorbia supina Raf. (ESR) was found to exert the highest potency to attenuate cell death caused by treatment of DEPs. Our liquid chromatography-mass spectrometry analysis showed that DEPs-mediated increase in ceramide production was slightly attenuated in cells treated with both ESR. Interestingly, whereas, S1P generation was dramatically elevated in cells treated with ESR. Finally, we found that ESR contains phenolic compounds, such as methyl gallate, quercetin, and kaempferol, as an active constituent. Together, these results suggest that the phenolic compounds present in ESR could protect cells against the DEPs-mediated apoptosis by enhancing metabolic conversion of ceramide to S1P.