{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:20:56Z","timestamp":1774520456699,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with <jats:italic>ELANE<\/jats:italic> variants and severe congenital neutropenia (SCN) commonly develop oral complications. Whether they are caused only by low neutrophil count or the combination of neutropenia and aberrant dental cells is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genetic variant was identified with exome sequencing. Dental pulp cells isolated from the SCN patient with an <jats:italic>ELANE<\/jats:italic> mutation were investigated for gene expression, enzyme activity, proliferation, colony formation, wound healing, apoptosis, ROS, attachment, spreading and response to lipopolysaccharide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ELANE cells had diminished expression of <jats:italic>ELANE<\/jats:italic> and <jats:italic>SLPI<\/jats:italic> and reduced neutrophil elastase activity. Moreover, ELANE cells exhibited impaired proliferation, colony forming, migration, attachment and spreading; and significantly increased ROS formation and apoptosis, corresponding with increased <jats:italic>Cyclin D1<\/jats:italic> and <jats:italic>MMP2<\/jats:italic> levels. The intrinsic levels of <jats:italic>TGF<\/jats:italic>\u2010<jats:italic>\u03b21<\/jats:italic> and <jats:italic>TNF<\/jats:italic>\u2010<jats:italic>\u03b1<\/jats:italic> were significantly increased; however, <jats:italic>IL<\/jats:italic>\u2010<jats:italic>6<\/jats:italic>, <jats:italic>IL<\/jats:italic>\u2010<jats:italic>8<\/jats:italic> and <jats:italic>NF<\/jats:italic>\u2010<jats:italic>kB1<\/jats:italic> were significantly decreased in ELANE cells compared with those in controls. After exposure to lipopolysaccharide, ELANE cells grew larger, progressed to more advanced cell spreading stages and showed significantly increased <jats:italic>SLPI<\/jats:italic>, <jats:italic>TNF<\/jats:italic>\u2010<jats:italic>\u03b1 and NF<\/jats:italic>\u2010<jats:italic>kB1<\/jats:italic> and tremendously increased <jats:italic>IL<\/jats:italic>\u2010<jats:italic>6<\/jats:italic> and <jats:italic>IL<\/jats:italic>\u2010<jats:italic>8<\/jats:italic> expression, compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study, for the first time, suggests that in addition to neutropenia, the aberrant levels and functions of <jats:italic>ELANE<\/jats:italic>, <jats:italic>SLPI<\/jats:italic> and their downstream molecules in pulp cells play an important role in oral complications in SCN patients. In addition, pulp cells with diminished neutrophil elastase and SLPI are highly responsive to inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13132","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T02:10:41Z","timestamp":1632795041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Reduced ELANE and SLPI expression compromises dental pulp cell activity"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-1983","authenticated-orcid":false,"given":"Kanokwan","family":"Sriwattanapong","sequence":"first","affiliation":[{"name":"Genomics and Precision Dentistry Research Unit Department of Physiology Faculty of Dentistry Chulalongkorn University  Bangkok 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