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Impact of air pollutants on cutaneous responses in both healthy and compromised skin barrier, and innovative solutions to protect skin against urban pollution

Periodic Reporting for period 1 - CITYCARE (Impact of air pollutants on cutaneous responses in both healthy and compromised skin barrier, and innovative solutions to protect skin against urban pollution)

Reporting period: 2017-09-01 to 2019-08-31

The skin is the first barrier against the external environment. Hence, it is constantly exposed to oxidative stress from pollutants such as ground level ozone (O3), particulate matter, cigarette smoke and solar radiation. Those pollutants have severe impacts on skin, including premature skin aging and cancer, as well as may aggravate skin diseases such as eczema, psoriasis and urticaria.
The CITYCARE project aims at better understanding the effects of air pollutants on both skin barrier integrity and function by investigating the synergistic effects of air pollutants such as ozone, cigarette smoke and diesel exhaust with UV radiation. Since the percentage of the world’s population being urban is continuously increasing, there is an urgent need to protect every single city dweller from urban pollution. Although the use of sunscreens in skin care formulations provides an essential protection against the cutaneous damages caused by UV radiation, there is to date not a single class of compounds that have been identified to protect skin against the whole spectrum of environmental stressors. For this reason, an important part of the project includes the study and the testing of innovative solutions to protect skin against those air pollutants using both antioxidant compounds and film forming polymers as protective approaches.
To study the effects of environmental pollutants at the skin level, a human epidermal equivalent (HEE) model mimicking the upper layer of the skin (i.e. the epidermis) was first developed. This HEE model consists of primary keratinocytes, the main cells present in the epidermis, that are cultivated on a supporting membrane for several weeks to obtain a multilayered epidermal tissue that resembles the healthy native human epidermis. Besides a healthy model, also a compromised barrier model was prepared, to investigate differences in the effects of air pollutants between healthy and altered skin conditions. These two HEE models were fully characterized using common cell culture techniques to guarantee that they resemble the main features of intact and impaired human skin.
Besides the reproducibility and the overall morphology of the human epidermal equivalents, also their responsiveness to different stimuli was investigated. In this way, the correct positive controls for assays to study the cytotoxicity, mitochondrial activity, tissue integrity and pro-inflammatory response were determined. After establishing relevant human epidermal models, exposure conditions to the several air pollutants were optimized. Additional studies are now carried out to have a deeper understanding about how these pollutants, combined or not with solar radiation, are affecting the skin. Direct and indirect effects of these pollutants are investigated.
Creating human exposure data based on non-animal approaches became now a requirement in the process of risk and hazard assessment. The reconstructed epidermis is the first organ that received regulatory approval for irritation testing. Indeed, 3D skin models based on cells of human origin mimic more closely the native human skin and its response to exogenous chemicals. However, there are still few investigations about the effect of air pollutants on 3D skin models.
Air pollutants of main health concern include ozone, diesel particles and cigarette smoke. Therefore, three exposure systems have been designed in order to mimic the human exposure in the most realistic conditions. Using the same HEE, a comparison between the post-exposure biological responses to the different air pollutants is possible.
Expected results include a better understanding of the cutaneous toxicity induced by three main air pollutants combined or not with solar irradiation to better counteract it with the help of protective or curative solutions, respectively film forming polymers or antioxidants compounds. In addition, mechanistic studies might give insights in the development of therapeutic solutions to fight against air pollution induced skin disorders.
Finally, the project aims at increasing the awareness of urban citizens about the involvement of air pollution in the development or exacerbation of skin diseases.
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