PMID- 29066283 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20180920 IS - 0925-4439 (Print) IS - 0925-4439 (Linking) VI - 1864 IP - 1 DP - 2018 Jan TI - The extent of pyroptosis varies in different stages of apical periodontitis. PG - 226-237 LID - S0925-4439(17)30389-7 [pii] LID - 10.1016/j.bbadis.2017.10.025 [doi] AB - Apical periodontitis (AP) is an inflammation affecting the periapical region of tooth root. Microbial pathogens activate inflammasomes and promote the production of pro-inflammatory cytokines. Caspase-1-mediated pyroptosis is a possible mechanism involved in the initiation and progression of AP. The purpose of this study was to evaluate the role of caspase-1 and pyroptosis on AP at different stages. Human periapical inflammatory tissue was collected to study chronic AP stage. Human periodontal ligament fibroblasts (hPDLFs) were stimulated with lipopolysaccharide in vitro for 24h to simulate early AP stage. Experimental AP rat model was established to study acute AP stage from 0d to 28d. The results showed that NLRP3, cleaved caspase-1 and Interleukin (IL)-1beta were enhanced in all AP stages. Caspase-1 activation was detectable in most cells. However, the level of pyroptosis was in accordance with the degree of AP inflammation. Early and chronic AP showed a comparable hemostasis state, with pyroptosis remaining in a reduced level. On the contrary, extensive pyroptosis accelerated inflammation and induced cell death in acute AP. VX765, a caspase-1 inhibitor, was used in an experimental AP rat model. The results showed that VX765 suppressed bone loss, suggesting a role of pyroptosis on bone resorption in acute AP. VX765 also inhibited the expressions of IL-1beta, Monocyte chemoattractant protein-1 (MCP-1), IL-6 and IL-8 in vitro, thus decreased inflammatory responses during AP. In conclusion, caspase-1 and pyroptosis contributed to AP inflammation and lesion and pyroptosis extent was in line with AP progression. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Cheng, Ran AU - Cheng R AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. FAU - Feng, Yuchao AU - Feng Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. FAU - Zhang, Rui AU - Zhang R AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. FAU - Liu, Wen AU - Liu W AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. FAU - Lei, Lei AU - Lei L AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. FAU - Hu, Tao AU - Hu T AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. Electronic address: hutao@scu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171021 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Caspase 1/physiology MH - Cells, Cultured MH - Disease Progression MH - Female MH - Fibroblasts/pathology/physiology MH - Humans MH - Periapical Periodontitis/*pathology MH - Periodontal Ligament/pathology MH - Pyroptosis/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Severity of Illness Index OTO - NOTNLM OT - Caspase-1 OT - IL-1beta OT - Microbial-cell interaction OT - Pyroptosis OT - hPDLFs EDAT- 2017/10/27 06:00 MHDA- 2018/03/27 06:00 CRDT- 2017/10/26 06:00 PHST- 2017/08/15 00:00 [received] PHST- 2017/10/02 00:00 [revised] PHST- 2017/10/19 00:00 [accepted] PHST- 2017/10/27 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2017/10/26 06:00 [entrez] AID - S0925-4439(17)30389-7 [pii] AID - 10.1016/j.bbadis.2017.10.025 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):226-237. doi: 10.1016/j.bbadis.2017.10.025. Epub 2017 Oct 21.