Hypoxia-induced NLRP3 inflammasome activation via the HIF-1α/NF-κB signaling pathway in human dental pulp fibroblasts

作者：Diya Wang, Minghao Wang, Shukai Sun, Chongyang Zhang, Song Ya, Jianing Li, Bing Song, Haipeng Lv, Shengchao Wang, Wenkai Jiang · 发表于：BMC Oral Health · 年份：2024 · DOI：10.1186/s12903-024-04936-w · 被引用次数：25 · 研究领域：Endodontics and Root Canal Treatments、Dental Erosion and Treatment、Pneumothorax, Barotrauma, Emphysema

BACKGROUND: Previous studies have reported the link between hypoxic conditions and NLRP3 inflammasome-mediated pulpal inflammation in the progression of pulpitis. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the role of HIF-1α in the regulation of NLRP3 inflammasome pathway via NF-κB signaling under hypoxic conditions with or without LPS in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. METHODS: HIF-1α plasmids or siRNAs were used to upregulate or downregulate HIF-1α in HDPFs, respectively. The effect of hypoxia with or without LPS on the NF-κB signaling and NLRP3 inflammasome pathway was analyzed by immunofluorescence staining, qRT-PCR, western blotting and ELISA. RESULTS: The hypoxic conditions alone induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling in a time-dependent manner in HDPFs. The upregulation of HIF-1α further promoted hypoxia-induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. In comparison, downregulation of HIF-1α inhibited ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Additionally, LPS plus hypoxia further promoted HIF-1α expression and NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. CONCLUSIONS: HIF-1α served as a pos...