{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:11:09Z","timestamp":1788297069708,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670994 and 81900993"],"award-info":[{"award-number":["31670994 and 81900993"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To explore the presence and function of NLRP6\u2010caspase 4 inflammasome in human pulp tissue and human dental pulp cells (HDPCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Pulp tissue was collected from freshly extracted human caries\u2010free third molars and third molars with irreversible pulpitis. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) and western blot were performed to assess the expression of NLRP6\u2010caspase 4 inflammasome. HDPCs were prepared from normal human pulp tissues and challenged with <jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS. Enzyme\u2010linked immunosorbent assay (ELISA) and qRT\u2010PCR were performed to assess if LPS can upregulate NLRP6 and caspase\u20104. HDPCs were further challenged with LPS followed with cytosolic <jats:italic>Streptococcus mutans<\/jats:italic> lipoteichoic acid (LTA). SiRNA targeting <jats:italic>NLRP6<\/jats:italic> and <jats:italic>Casp4<\/jats:italic> and pharmacology inhibitor Ac\u2010FLTD\u2010CMK and MCC950 were used to assess if <jats:italic>Streptococcus mutans<\/jats:italic> LTA can activate the NLRP6 but not the NLRP3 inflammasome. Western blot and ELISA were performed to evaluate inflammasome activation. The Student\u2019s <jats:italic>t<\/jats:italic>\u2010test and one\u2010way <jats:sc>anova<\/jats:sc> were used for statistical analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NLRP6\u2010caspase 4 inflammasome was upregulated and activated in inflamed human dental pulp tissue. In HDPCs, <jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS upregulated the expression of <jats:italic>NLRP6<\/jats:italic>, <jats:italic>CASP1<\/jats:italic> and <jats:italic>CASP4<\/jats:italic> in a type I interferon dependent manner. After LPS priming, cytosolic <jats:italic>Streptococcus mutans<\/jats:italic> LTA triggered NLRP6\u2010caspase 4 inflammasome activation. Knockdown of <jats:italic>NLRP6<\/jats:italic> or <jats:italic>CASP4<\/jats:italic> using siRNA or using pharmacology inhibitor Ac\u2010FLTD\u2010CMK but not MCC950 efficiently suppressed inflammasome activation by cytosolic LTA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NLRP6\u2010caspase 4 inflammasome may play an important role in pulp inflammation and immune defence. Inflammatory caspases represent a pharmacological target to restrain pulpal inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13469","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T11:54:27Z","timestamp":1609329267000},"page":"916-925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["NLRP6\u2010caspase 4 inflammasome activation in response to cariogenic bacterial lipoteichoic acid in human dental pulp inflammation"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-1291","authenticated-orcid":false,"given":"X. X.","family":"Tian","sequence":"first","affiliation":[{"name":"Stomatology Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatology Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Neuroradiology The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Liu","sequence":"additional","affiliation":[{"name":"Stomatology Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Stomatology Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. P.","family":"Wang","sequence":"additional","affiliation":[{"name":"Stomatology Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. L.","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases Department of Cariology and Endodontics West China Hospital of Stomatology Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00046-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2020.06.008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0277-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190111"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-020-0256-z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.047"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-2399(97)80205-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1236381"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.06.026"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-015-2118-7"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp017"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.01.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13091"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.97"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-2399(06)80032-4"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2007.05.018"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112306"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0143-2885.2004.00782.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.30"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.09.023"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511405390"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004770-200104000-00008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.026"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767318095296"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800562115"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104794"}],"container-title":["International Endodontic Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iej.13469","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/iej.13469","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iej.13469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T13:19:34Z","timestamp":1693142374000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iej.13469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,20]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/iej.13469"],"URL":"https:\/\/doi.org\/10.1111\/iej.13469","archive":["Portico"],"relation":{},"ISSN":["0143-2885","1365-2591"],"issn-type":[{"value":"0143-2885","type":"print"},{"value":"1365-2591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,20]]},"assertion":[{"value":"2020-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}