Diesel Particulate Extract Accelerates Premature Skin Aging in Human Fibroblasts via Ceramide-1-Phosphate-Mediated Signaling Pathway

Abstract

Both intrinsic (i.e., an individual’s body clock) and extrinsic factors (i.e., air pollutants and ultraviolet irradiation) accelerate premature aging. Epidemiological studies have shown a correlation between pollutant levels and aging skin symptoms. Diesel particle matter in particular leads to some diseases, including in the skin. Our recent study demonstrates that diesel particulate extract (DPE) increases apoptosis via increases in an anti-mitogenic/pro-apoptotic lipid mediator, ceramide in epidermal keratinocytes. Here, we investigated whether and how DPE accelerates premature skin aging using cultured normal human dermal fibroblasts (HDF). We first demonstrated that DPE increases cell senescence marker β-galactosidase activity in HDF. We then found increases in mRNA and protein levels, along with activity of matrix metalloprotease (MMP)-1 and MMP-3, which are associated with skin aging following DPE exposure. We confirmed increases in collagen degradation in HDF treated with DPE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is activated by DPE and results in increased ceramide production by sphingomyelinase activation in HDF. We identified that ceramide-1-phosphate (C1P) (produced from ceramide by ceramide kinase activation) activates MMP-1 and MMP-3 through activation of arachidonate cascade, followed by STAT 1- and STAT 3-dependent transcriptional activation.

Effects of Air Pollution on Cellular Senescence and Skin Aging

“…The composition of atmospheric pollution can also vary depending on the time of day, seasons, human activity, and geographic location [ 8 , 9 ]. Several reports suggest that air pollutant components are direct contributors to the process of aging [ 5 , 11 , 79 , 80 , 81 , 82 ]. Human exposition to air pollution contributes to increased mortality and hospital stays.…”

“…ROS generation, induced by exposure of the skin to air pollution, can induce MMPs expression and increase their activity, especially MMP-1 and MMP-3 which are known to accelerate the skin aging process by degrading collagen and elastin. Additionally, the decreased expression of transforming growth factor (TGF) β, and reduced synthesis of collagen type 1 α chain ( COL1A1, COL1A2 ) and elastin by fibroblasts are other contributors to the formation of wrinkles and skin aging induced by PM [ 80 , 82 , 102 ].…”

“…Exposition of the skin to cigarette smoke induces oxidative stress and the impairment of the antioxidant system. The consequences are transepidermal water loss, lipid peroxidation, cell death, and degeneration of connective tissue by MMP-1 and -3 [ 80 , 114 , 116 ]. In keratinocytes, cellular redox homeostasis and colony-forming potential was affected in response to exposure to tobacco smoke components such as PAH and PM [ 92 ].…”

“…These results demonstrate that PM-induced skin aging can be triggered by epigenetic modifications which could give rise to new strategies for therapeutics against skin aging. Skin cells exposed to diesel particulate extract (DPE), which mainly contains PM and PAH [103], displayed dysregulation of proteins and lipids important for the maintenance of skin integrity, for the regulation of skin hydration and oxidative stress, such as NADPH oxidase (NOX), ceramide, plakins, transglutaminases, cystatins, and filaggrin [57,80]. Furthermore, DPE impaired mitochondrial oxidative phosphorylation and cell migration in these cells.…”

Lipid Peroxidation as the Mechanism Underlying Polycyclic Aromatic Hydrocarbons and Sunlight Synergistic Toxicity in Dermal Fibroblasts

“…At the epidemiological level, a correlation has been found between signs of skin aging and people living in polluted areas [1]. At the molecular level, exposure to cigarette smoke and diesel particulate extracts has been associated with an increase in MMP1 and MMP3 and a decrease in collagen neo-synthesis [36,37]. Human dermal fibroblasts exposed to particulate matters showed a decrease in cell viability, and an increase in MMP-1 and MMP-3 associated with a decrease in pro-collagen, TGF-β and elastin gene expression [38].…”