706 Ceramide-1-phosphate accelerates premature skin aging in skin fibroblasts exposed to diesel particulate extract

Extrinsic factors, such as air pollutants and ultraviolet irradiation (UVR), accelerate premature aging, a correlation between levels of skin aging symptoms has been reported. Diesel particulate matter, major source pollution, helps initiate some diseases, including diseases. We recently demonstrated that diesel extract (DPE) activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), followed by activation sphingomyelinase (SMase), leading to ceramide (Cer) production in cultured normal keratinocytes (KC). characterized increases Cer-dependent lipid mediator induces apoptosis. Using human dermal fibroblasts (HDF), here we investigated whether/how DPE accelerates aging. Non-toxic concentrations increased cell senescence marker ß-galactosidase activity HDF. Following exposure, found mRNA/protein expression matrix metalloprotease (MMP)-1 MMP-3 activities, which are all associated with NOX was activated resulted Cer due SMase next asked whether or its metabolites (Cer-1-phosphate [C1P] sphingosine-1-phosphate [S1P]) promotes MMP-1/MMP-3 activation. inhibition kinase, but not sphingosine kinase suppressed activation, identified C1P via initiation an arachidonate pathway activating cPLA2, STAT1- STAT3-dependent transactivation. confirmed type 1 collagen degradation HDF DPE-mediated C1P-dependent pathway. is also only DPE, other external/internal stressors; i.e., UVR, cigarette smoke, inflammatory cytokines. Our evidence above points playing critical role response diverse stressors.