Korean Red Ginseng Attenuates Particulate Matter-Induced Senescence of Skin Keratinocytes.

Skin is a direct target of fine particulate matter (PM), as it is constantly exposed. Herein, we investigate whether Korean red ginseng (KRG) can inhibit PM-induced senescence in skin keratinocytes. PM-treated human keratinocyte cell lines and normal human epidermal keratinocytes showed characteristics of cellular senescence, including flat and enlarged forms; however, KRG suppressed them in both cell types. Moreover, while cells exposed to PM showed a higher level of p16 expression (a senescence inducer), KRG inhibited its expression. Epigenetically, KRG decreased the expression of the ten-eleven translocation (TET) enzyme, a DNA demethylase induced by PM, and increased the expression of DNA methyltransferases suppressed by PM, resulting in the decreased methylation of the promoter region. Additionally, KRG decreased the expression of mixed-lineage leukemia 1 (MLL1), a histone methyltransferase, and histone acetyltransferase 1 (HAT1) induced by PM. Contrastingly, KRG increased the expression of the enhancer of zeste homolog 2, a histone methyltransferase, and histone deacetyltransferase 1 reduced by PM. Furthermore, KRG decreased TET1, MLL1, and HAT1 binding to the promoter, corresponding with the decreased mRNA expression of p16. These results suggest that KRG exerts protection against the PM-induced senescence of skin keratinocytes via the epigenetic regulation of .