PMID- 29028630 OWN - NLM STAT- MEDLINE DCOM- 20180815 LR - 20180815 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 85 DP - 2018 Jan TI - EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors. PG - 16-22 LID - S0003-9969(17)30323-0 [pii] LID - 10.1016/j.archoralbio.2017.10.004 [doi] AB - OBJECTIVE: Pulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues. METHODS: The expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-alpha were examined by quantitative real-time polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental pulp tissues were verified by histology. We invested the mechanisms of the effect of EZH2 on the inflammatory factors by ChIP assay. RESULTS: EZH2 down-regulation inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15, CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the promotion of inflammatory factors that were induced by rhTNF-alpha. In pulpitis models of rats, EZH2 down-regulation inhibited the inflammatory process of dental pulp while EZH2 complex showed no significant facilitation of pulpal inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and CCL2, but not IL-15 and CXCL12, to affect the transcription of these proinflammatory cytokines. CONCLUSIONS: In HDPCs, EZH2 could induce inflammation, while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays an important role in this inflammatory process of dental pulp. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Hui, Tianqian AU - Hui T AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Peking University, Beijing, China. FAU - A, Peng AU - A P AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. FAU - Zhao, Yuan AU - Zhao Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. FAU - Yang, Jing AU - Yang J AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. FAU - Ye, Ling AU - Ye L AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. FAU - Wang, Chenglin AU - Wang C AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: wxonet@163.com. LA - eng PT - Journal Article DEP - 20171007 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Cytokines) RN - EC 2.1.1.43 (EZH2 protein, human) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Chromatin Immunoprecipitation MH - Cytokines/*metabolism MH - Dental Pulp/*cytology MH - Disease Models, Animal MH - Down-Regulation MH - Enhancer of Zeste Homolog 2 Protein/*pharmacology MH - Humans MH - Immunohistochemistry MH - Pulpitis/*drug therapy/*metabolism MH - Rats MH - Real-Time Polymerase Chain Reaction OTO - NOTNLM OT - Chemokines OT - Dental pulp inflammation OT - EZH2 OT - Inflammatory factors OT - Interleukins EDAT- 2017/10/14 06:00 MHDA- 2018/08/16 06:00 CRDT- 2017/10/14 06:00 PHST- 2017/04/11 00:00 [received] PHST- 2017/09/22 00:00 [revised] PHST- 2017/10/07 00:00 [accepted] PHST- 2017/10/14 06:00 [pubmed] PHST- 2018/08/16 06:00 [medline] PHST- 2017/10/14 06:00 [entrez] AID - S0003-9969(17)30323-0 [pii] AID - 10.1016/j.archoralbio.2017.10.004 [doi] PST - ppublish SO - Arch Oral Biol. 2018 Jan;85:16-22. doi: 10.1016/j.archoralbio.2017.10.004. Epub 2017 Oct 7.