AIR PARTICULATE MATTER INDUCES SKIN BARRIER DYSFUNCTION AND WATER TRANSPORT ALTERATION ON A RECONSTRUCTED HUMAN EPIDERMIS MODEL.

Abstract Knowing the damage that PM can lead to skin is important to a tight control of air pollutants release and to prevent more serious diseases. This study investigates if such alterations are present in a Reconstructed Human Epidermis (RHE) exposed to PM10. Following exposure of RHE to increasing concentrations (2.2, 8.9 and 17.9 μg/cm2) of a standard Urban Particulate Matter over time, led to decreased cell viability at 48 hours. The barrier function was shown to be compromised by 24 hours of exposure to high doses (17.9 μg/cm2). Morphological alterations included cytoplasm vacuolization and partial loss of epidermal stratification. Cytokeratin 10, involucrin, loricrin and filaggrin protein levels were significantly decreased. We confirmed an inflammatory process by IL-1α release and found a significant increase in Aquaporin-3 (AQP3) expression. We also demonstrated changes in NOTCH1 and AhR expression of epidermis treated with PM10. The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cysteine (NAC) altered NOTCH1 expression, evidencing this is a redox-dependent process. These results demonstrate coarse PM10 induces dose-dependent inflammatory response and alterations in proteins markers of differentiation and water transport in the epidermis that could ultimately compromise the structural integrity of the skin, promoting or exacerbating various skin diseases.