Bibliographic Details
| Title: |
Hypoxia-induced NLRP3 inflammasome activation via the HIF-1α/NF-κB signaling pathway in human dental pulp fibroblasts |
| Authors: |
Diya Wang, Minghao Wang, Shukai Sun, Chongyang Zhang, Ya Song, Jianing Li, Bing Song, Haipeng Lv, Shengchao Wang, Wenkai Jiang |
| Source: |
BMC Oral Health, Vol 24, Iss 1, Pp 1-10 (2024) |
| Publisher Information: |
BMC, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Dentistry |
| Subject Terms: |
NLRP3, HIF-1α, Human dental pulp fibroblasts, Pulpitis, Sterile inflammation, Dentistry, RK1-715 |
| More Details: |
Abstract 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 positive regulator of NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling in HDPFs in the sterile pulpal inflammation and caries-related pulpitis microenvironment. The finding of a novel functional HIF-1α-NF-κB-NLRP3 axis provides insight into the link between the hypoxic microenvironment and pulpal inflammation, thus supporting a promising therapeutic strategy for the control of pulpal inflammation. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1472-6831 |
| Relation: |
https://doaj.org/toc/1472-6831 |
| DOI: |
10.1186/s12903-024-04936-w |
| Access URL: |
https://doaj.org/article/d97de4a8153646e8a09030ea1cfc415f |
| Accession Number: |
edsdoj.97de4a8153646e8a09030ea1cfc415f |
| Database: |
Directory of Open Access Journals |
