Abstract：
The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide-release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 μm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM-exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders.
摘要：
空气污染对健康的影响正在获得越来越多的研究兴趣，有关皮肤改变的数据有限。有人建议空气污染是敏感皮肤（SS）的触发因素。然而,该数据基于缺乏实验数据的调查。SS与改变的皮肤神经末梢和皮肤神经源性炎症有关。本研究旨在评估颗粒物（PM）对表皮和神经末梢稳态的体外作用。根据经验证的方案收集PM样品。重建人类表皮(RHE，将Episkin®）暴露于PM，随后将上清液转移到分化成感觉神经元（SN）的PC12细胞培养物中。细胞活力，测量轴突生长和神经肽释放。不同炎症表达的调节,评估角质形成细胞分化和神经突生长标志物。PM样品含有高比例的尺寸小于1μm的颗粒和复杂的化学组成。转录组学和免疫组织化学分析表明，PM改变了角质形成细胞的终末分化并诱导了炎症反应。虽然SN的生存能力和功能没有被修改，与暴露于PM的Episkin®上清液孵育后,它们的长出显著减少.这与神经生长因子/信号素3A平衡的改变密切相关。这项研究表明，空气污染物对角质形成细胞和感觉神经末梢有负面影响，包括炎症反应。这些作用可能与SS的病理生理学有关，也可能与炎症性皮肤病有关。
