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Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway
| Content Provider | Scilit |
|---|---|
| Author | Huang, Cancan Zhang, Chaotao Yang, Panpan Chao, Rui Yue, Ziqi Li, Congshan Guo, Jie Li, Minqi |
| Copyright Year | 2020 |
| Description | Purpose: Periodontitis is a major chronic oral disease that is accelerated by activation of the NLRP3 inflammasome and the resulting pyroptosis. According to recent studies, active vitamin D and its analogs have been reported to have great anti-inflammatory effects. However, the anti-inflammatory mechanism of a newly found vitamin D analog, eldecalcitol (ED-71), is still unclear. This study investigates whether ED-71 could protect human gingival fibroblasts (HGFs) from LPS-induced pyroptosis and, if so, determine its underlying mechanism. Methods: After HGFs were treated with LPS alone or with LPS and ED-71, their viability was measured by CCK8 assay. The degrees of inflammation and pyroptosis were measured via LDH assay, $H_{2}O_{2}$ assay, fluorescent staining, flow cytometry, and Western blots. Intracellular ROS, Hoechst 33,342, and PI stains were assessed with a fluorescence microscope. ROS inhibitor NAC, NLRP3 inhibitor MCC950, and Nrf2 inhibitor ML385 were added to further clarify the mechanism. Results: LPS induced cytotoxicity in HGFs, as shown by CCK8 assay. LPS also increased intracellular ROS, $H_{2}O_{2}$ levels, release of LDH, and expression of the pyroptosis-related proteins NLRP3, caspase-1, and IL-1β. NAC and MCC950 reduced LPS-induced NLRP3, caspase-1, and IL-1β. Pretreatment with ED-71 effectively inhibited the LPS-induced pyroptosis and was associated with activation of the Nrf2/HO-1 signaling pathway. This beneficial effect of ED-71 was suppressed by ML385. Conclusion: This study demonstrates the therapeutic effect of ED-71 on LPS-induced NLRP3 inflammasome-dependent pyroptosis in HGFs and further reveals that ED-71 can inhibit pyroptosis by activating the Nrf2/HO-1 pathway. Our results thus suggest that ED-71 is a potential candidate for the treatment of periodontitis. |
| Related Links | https://www.dovepress.com/getfile.php?fileID=63723 |
| Ending Page | 4913 |
| Page Count | 13 |
| Starting Page | 4901 |
| e-ISSN | 11778881 |
| DOI | 10.2147/dddt.s269223 |
| Journal | Drug design, development and therapy |
| Volume Number | 14 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2020-11-01 |
| Access Restriction | Open |
| Subject Keyword | Dentistry and Oral Surgery Pyroptosis Ed-71 Nrf2/ho-1 |
| Content Type | Text |
| Resource Type | Article |
