Protective role of calcitriol in PM2.5-induced apoptosis and inflammation in bronchial epithelial cells in vitro via vitamin D receptor-mediated Nrf2 signaling.

内容摘要

PM2.5 contributes to lung injury by inducing oxidative stress, inflammatory responses, and apoptosis. Calcitriol exerts a protective role against lung injury by regulating the vitamin D receptor (VDR) and Nrf2 signaling pathways, mitigating PM2.5-induced oxidative stress and inflammation. In this study, we investigated the protective effects of calcitriol against PM2.5-induced apoptosis, oxidative damage, and inflammation in human bronchial epithelial BEAS-2B cells, with a specific focus on the crosstalk between VDR and Nrf2 signaling. BEAS-2B cells were pre-treated with calcitriol (1, 10, 100 nM) for 24 h before PM2.5 exposure (100 µg/mL). Apoptosis, DNA damage, and inflammation were assessed by flow cytometry, ELISA, qRT-PCR, and Western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate VDR-antioxidant response element (ARE) binding. Calcitriol suppressed apoptotic signaling by reducing p53 phosphorylation and downregulating the mRNA expression of p53 and caspase-3, while also mitigating oxidative DNA damage, as indicated by decreased levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in BEAS-2B cells. Additionally, calcitriol suppressed inflammatory responses by downregulating NF-κB activity and the mRNA expression of NF-κB p65 and its downstream pro-inflammatory genes, including IκB-α, TNF-α, and IL-6. Moreover, calcitriol treatment increased VDR protein expression and enhanced Nrf2 activity. ChIP assays demonstrated that calcitriol enhanced VDR binding to AREs, thereby promoting the transcription of key Nrf2-regulated cytoprotective genes, including heme oxygenase-1 (HO-1) and NADPH quinone dehydrogenase 1 (NQO1). These findings provide mechanistic insight into the pharmacological effects of calcitriol, underscoring its potential to alleviate PM2.5-induced cellular injury through VDR-mediated activation of Nrf2 redox signaling.