Fig. 2

The main affected pathways upon exposure of the skin to airborne PM. (A) PM disrupts the barrier of skin with an already existing barrier dysfunction to a greater extent. (B) The underlying mechanism of the effects of PM exposure on the skin. PM can disrupt the epidermal barrier by increasing the levels of antimicrobial peptides (AMP) and inhibiting the levels of proteins that are essential for cell differentiation and proliferation (i.e., FLG: Filaggrin, LOR: Loricrin, KERs: Keratins). PM induces both exogenous ROS (exROS) and endogenous ROS (ROS) formation by activation of the aryl hydrocarbon receptor (AhR), upon exposure to polycyclic hydrocarbons (PAHs), and increased activity of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes (NOX). A misbalance of ROS and antioxidant scavengers results in oxidative stress. ROS activates the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to propagate oxidative stress, by inducing the gene transcription of glutathione S-transferase (GST), heme oxygenase 1 (HMOX1), and NAD(P) H quinone dehydrogenase 1 (NQO1). ROS can cause damage to the skin by lipid peroxidation, protein carbonylation, and can cause irreversible cellular impairment through DNA damage. These damages, together with mitochondrial dysfunction, can lead to apoptosis. PM can activate the Toll-like receptor (TLR), leading to activation of the mitogen-activated protein kinase (MAPK) pathway and the nuclear factor kappa B (NF-κB) pathway. This, in turn, leads to an upregulation of gene expression of cytokines such as tumor necrosis factor (TNF), interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), as well as, chemokines such as C-X-C motif chemokine ligand 8 (CXCL8), adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), enzymes such as cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and matrix metalloproteases (MMPs). Fig. A is adapted with permission from van Smeden et al. and elements have been used for Fig. B [247]