Abstract
Background: The exposure of the human skin to particulate matter 2.5 (PM(2.5)) results in adverse health outcomes, such as skin aging, wrinkle formation, pigment spots, and atopic dermatitis. It has previously been shown that rosmarinic acid (RA) can protect keratinocytes from ultraviolet B radiation by enhancing cellular antioxidant systems and reducing oxidative damage; however, its protective action against the adverse effects of PM(2.5) on skin cells remains unclear. Therefore, in this study, we explored the mechanism underlying the protective effects of RA against PM(2.5)-mediated oxidative stress in HaCaT keratinocytes. Methods: HaCaT keratinocytes were pretreated with RA and exposed to PM(2.5). Thereafter, reactive oxygen species (ROS) production, protein carbonylation, lipid peroxidation, DNA damage, and cellular apoptosis were investigated using various methods, including confocal microscopy, western blot analysis, and flow cytometry. Results: RA significantly inhibited PM(2.5)-induced lipid peroxidation, protein carbonylation, DNA damage, increases in intracellular Ca(2+) level, and mitochondrial depolarization. It also significantly attenuated PM(2.5)-induced apoptosis by downregulating Bcl-2-associated X, cleaved caspase-9, and cleaved caspase-3 protein levels, while upregulating B-cell lymphoma 2 protein level. Further, our results indicated that PM(2.5)-induced apoptosis was associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and that MAPK inhibitors as well as RA exhibited protective effects against PM(2.5)-induced apoptosis. Conclusion: RA protected HaCaT cells from PM(2.5)-induced apoptosis by lowering oxidative stress.