Particulate pollution acts on epidermis through pathways that are distinct from intrinsic or UV-induced aging

Summary: Abstract Body: Epidermal permeability barrier disruption increases not only skin inflammation but also systemic inflammation via skin-derived cytokines such as IL-6 and TNF-alpha. Particulate pollution (PM2.5) is an important source of systemic inflammation, but whether cutaneous exposure to PM2.5 might contribute to systemic effects is, as yet, unknown. Recently, we reported that aged skin suffers from increased PM2.5 penetration without increased transepidermal water loss (TEWL), likely due to larger but more widely spaced stratum corneum defects, which could be reproduced in young mice by occlusion or microneedle application. Using diesel particulate extract (DPE), we first found that DPE's actions on keratinocyte extrinsic aging induce genes that differ from intrinsic aging, as well as differing from aging induced by sequential passaging and aging induced by UV radiation. With bulk RNAseq, we identified known and novel pathways of DPE action, including reactive oxygen pathways and endoplasmic reticulum stress pathways. These findings demonstrate that PM2.5 acts to induce extrinsic skin aging through pathways that differ from intrinsic aging and aging induced by UV, suggesting that increased aged skin permeability may make aged skin more susceptible to DPE effects, and the combination of intrinsic aging and DPE may induce more inflammatory cytokines than either factor alone. Lastly, these findings suggest that ameliorating DPE actions on skin may improve both skin health and systemic health in people exposed to particulate pollution. Anna Celli¹, T R. Parenteau¹, Yuko Oda², Jeffrey Cheng¹, Theodora Mauro¹ 1. Dermatology, University of California San Francisco, San Francisco, CA, United States. 2. Endocrinology, University of California San Francisco, San Francisco, CA, United States. Epidermal Structure and Barrier Function