Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
Exp Dermatol. 2019 Jul;28(7):809-815. doi: 10.1111/exd.13943. Epub 2019 May 15.
Particulate matter (PM) is known to have harmful effects on human health. Epidemiological studies have suggested that PM exposure is related to skin diseases and extrinsic skin ageing. However, the mechanisms by which PM affects skin are unclear. The aim of this study was to investigate the mechanism of action of PMs on epidermal inflammation and skin ageing using a co-culture of human keratinocytes (HaCaT) and fibroblasts (HDF). SRM 1648a (pmA) and 1649b (pmB), which mainly comprise heavy metals and polycyclic aromatic hydrocarbons, respectively, were used as reference PMs. Cytotoxic effects, activation of AhR, phosphorylation of p38 kinase and ROS generation were examined in PM-treated HaCaT cells. The phosphorylation of p38 MAPK induced by PMs was shown to be critically important for the increases in IL-1α and IL-1β expression. Moreover, the mRNA and protein expression levels of MMP1 and COX2 were markedly increased in HDF cells co-cultured with PM-treated HaCaT cells. In conclusion, PMs induce the expression of pro-inflammatory cytokines in keratinocytes via the p38 MAPK pathway, and these interleukins increase the expression of MMP1 and COX2 in HDF cells. These results suggest that PMs trigger skin ageing via p38 MAPK activation and interleukin secretion in epidermal keratinocytes.
颗粒物 (PM) 已知对人类健康有害。流行病学研究表明，PM 暴露与皮肤病和外源性皮肤老化有关。然而，PM 影响皮肤的机制尚不清楚。本研究旨在通过人角质形成细胞 (HaCaT) 和成纤维细胞 (HDF) 的共培养来研究 PM 对表皮炎症和皮肤老化的作用机制。分别使用主要包含重金属和多环芳烃的 SRM 1648a (pmA) 和 1649b (pmB) 作为参考 PM。在 PM 处理的 HaCaT 细胞中检查细胞毒性作用、AhR 激活、p38 激酶磷酸化和 ROS 生成。结果表明，PM 诱导的 p38 MAPK 磷酸化对于增加 IL-1α 和 IL-1β 的表达至关重要。此外，与 PM 处理的 HaCaT 细胞共培养的 HDF 细胞中 MMP1 和 COX2 的 mRNA 和蛋白表达水平明显增加。总之，PM 通过 p38 MAPK 通路诱导角质形成细胞中促炎细胞因子的表达，这些白细胞介素增加 HDF 细胞中 MMP1 和 COX2 的表达。这些结果表明，PM 通过表皮角质形成细胞中 p38 MAPK 的激活和白细胞介素的分泌引发皮肤老化。
