1,25-Dihydroxy Vitamin D Attenuates the Oxidative Stress-Mediated Inflammation Induced by PMvia the p38/NF-κB/NLRP3 Pathway.

Vitamin D is reported to be involved in the regulation of inflammatory processes. In this study, biomarkers related to oxidative stress and inflammation were investigated to clarify the protective effects and possible mechanism of 1,25-dihydroxy vitamin D (1,25-(OH)D) on PM-induced inflammatory response. In the in vitro study using human bronchial epithelial (HBE) cells, aqueous extracts of PM could induce oxidative damage which is characterized by significant increases in production of reactive oxygen species, malonaldehyde concentration, and protein expression of HSPA1A and HO-1. Meanwhile, PM caused secretion of inflammatory factors (IL-6, IL-8) in the culture medium as well as phosphorylation of p38, nuclear factor-kappa B (NF-κB) inhibitor alpha (IκBα), and NF-κB p65 proteins. Increases in NLRP3 expression was also observed in HBE cells after PM exposure. However, all these biomarkers were remarkably attenuated by a 24-h pretreatment of 1 nM 1,25-(OH)D. Furthermore, 1,25-(OH)D also reduced transcriptional activation of NF-κB induced by PM as indicated by a significant decrease in luciferase activity in HBE cells stably transfected with the NF-κB response element (RE)-driven luciferase reporter. Taken together, our findings provided novel experimental evidences supporting that vitamin D could reduce the predominantly oxidative stress-mediated inflammation induced by PMvia the p38/NF-κB/NLRP3 signaling pathway.