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In this study, we investigated the expression and role of BD2 in the amniotic membrane and human amniotic epithelial cells (hAECs) from patients with preterm birth and chorioamnionitis, focusing on its regulation of inflammatory cytokines and its protective effect on the epithelial barrier. Our results show increased BD2 expression in chorioamnionitis, and Lipopolysaccharide (LPS)-induced inflammation increased BD2 release from hAECs in a dose- and time-dependent manner. BD2 treatment effectively modulated the inflammatory response by reducing pro-inflammatory cytokines (IL-6, IL-1\u03b2) and enhancing the release of the anti-inflammatory cytokine IL-10. Additionally, BD2 helps preserve epithelial barrier integrity by restoring E-cadherin expression and reducing Snail expression in inflamed hAECs. In an LPS-induced preterm birth mouse model, BD2 treatment delayed preterm delivery and reduced inflammatory cytokine levels. These results suggest that BD2 plays a protective role in preventing preterm birth by regulating inflammation and maintaining epithelial barrier function, highlighting its therapeutic potential for inflammation-related preterm birth.<\/jats:p>","DOI":"10.3390\/ijms26052127","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T02:48:37Z","timestamp":1740710917000},"page":"2127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Beta-Defensin 2 in Preventing Preterm Birth with Chorioamnionitis: Insights into Inflammatory Responses and Epithelial Barrier Protection"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5677-5374","authenticated-orcid":false,"given":"Sangho","family":"Yun","sequence":"first","affiliation":[{"name":"Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-Hae","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwon","family":"Ryu","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoungseon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keun-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"},{"name":"Departments of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-7706","authenticated-orcid":false,"given":"Ji Young","family":"Hong","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"},{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Sacred Heart Hospital, Hallym University Medical Center, Chuncheon 24253, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga-Hyun","family":"Son","sequence":"additional","affiliation":[{"name":"Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea"},{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hemshekhar, M., Anaparti, V., and Mookherjee, N. 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