Biological effects of air pollution on the function of human skin equivalents

Abstract

The World Health Organization reports that 99% of the global population are exposed to pollution levels higher than the recommended air quality guidelines. Pollution‐induced changes in the skin have begun to surface; however, the effects require further investigation so that effective protective strategies can be developed. This study aimed to investigate some of the aging‐associated effects caused by ozone and particulate matter (PM) on human skin equivalents. Full‐thickness skin equivalents were exposed to 0.01 μg/μL PM, 0.05 μg/μL PM, 0.3 ppm ozone, or a combination of 0.01 μg/μL PM and 0.3 ppm ozone, before skin equivalents and culture medium were harvested for histological/immunohistochemical staining, gene and protein expression analysis using qPCR, Western blotting, and ELISA. Markers include MMP‐1, MMP‐3, COL1A1, collagen‐I, 4‐HNE, HMGCR, and PGE2. PM was observed to induce a decrease in epidermal thickness and an enhanced matrix building phenotype, with increases in COL1A1 and an increase in collagen‐I protein expression. By contrast, ozone induced an increase in epidermal thickness and was found to induce a matrix‐degrading phenotype, with decreases in collagen‐I gene/protein expression and increases in MMP‐1 and MMP‐3 gene/protein expression. Ozone was also found to induce changes in lipid homeostasis and inflammation induction. Some synergistic damage was also observed when combining ozone and 0.01 μg/μL PM. The results presented in this study identify distinct pollutant‐induced effects and show how pollutants may act synergistically to augment damage; given individuals are rarely only exposed to one pollutant type, exposure to multiple pollutant types should be considered to develop effective protective interventions.

Cutaneous Redox Senescence

“…Typically, these harmful effects are associated with decreased levels of antioxidants in the surface layers, such as vitamin E and vitamin C [99]. After exposure to the ozone, the product of lipid peroxidation in the stratum corneum activates phospholipases that release arachidonic acid [100,101], which is converted into several types of prostaglandins, especially PGE-2, a potent inflammatory mediator that promotes cellular senescence [102]. However, despite studies demonstrating an increase in PGE in senescent cells [103,104], there is still a gap in our knowledge about the mechanisms by which PGEs activate senescence in keratinocytes.…”

“…However, despite studies demonstrating an increase in PGE in senescent cells [103,104], there is still a gap in our knowledge about the mechanisms by which PGEs activate senescence in keratinocytes. An indication of a possible pathway for senescence activation via PGEs is due to the fact that they are considered part of the SASP, which is an important marker and initiator of cellular senescence and inflammatory processes [101], suggesting this pathway is the main senescence activation mechanism. Furthermore, studies with fibroblasts indicate the role of PGE-2 in inducing senescence [102,105].…”