{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:46:00Z","timestamp":1775695560512,"version":"3.50.1"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neutrophil extracellular traps (NETs) promote intra-acinar trypsin activation and tissue damage. Therefore, reducing NET formation can reduce tissue damage in severe acute pancreatitis (SAP). However, NET formation pathways may differ among disease models. In this study, we evaluated the role of the myeloperoxidase\u2013neutrophil elastase (NE) pathway in NET formation in SAP. SAP was induced by intraperitoneal injection of cerulein and LPSs in mice, and NE activity was inhibited by GW311616. Pancreatic tissues were collected for multiplex immunofluorescence, scanning electron microscopy, and western blotting to detect NET formation and the effect of NE on citrullinated histone H3, followed by analyses of serum amylase and cytokine levels. Pretreatment with GW311616 significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in SAP. Network pharmacology analyses using NE as the target revealed the monomeric compound epigallocatechin-3-gallate (EGCG). Binding between EGCG and NE was validated using molecular docking, and the ability of EGCG to inhibit NE activity was verified experimentally. NET formation by PMA-stimulated neutrophils was significantly reduced in vitro when the cells were pretreated with 40\u00a0\u03bcM EGCG. Pretreatment with EGCG significantly reduced NET formation, pancreatic tissue damage, and systemic inflammatory responses in vivo. These results reveal that NET formation requires the myeloperoxidase-NE pathway, and citrullination of histone H3 is affected by NE activity in SAP. EGCG shows therapeutic potential for affecting NE activity, NET formation, and systemic inflammation in SAP.<\/jats:p>","DOI":"10.1002\/jlb.3a0322-151r","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T08:05:14Z","timestamp":1660896314000},"page":"1427-1443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Epigallocatechin-3-gallate reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis"],"prefix":"10.1093","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-6235","authenticated-orcid":false,"given":"Hongxuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-1315","authenticated-orcid":false,"given":"Cong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-4625","authenticated-orcid":false,"given":"Lingyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingxu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-4805","authenticated-orcid":false,"given":"Dongbo","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-6702","authenticated-orcid":false,"given":"Yingmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"2023032107474401600_","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/S0140-6736(20)31310-6","article-title":"Acute pancreatitis","volume":"396","author":"Boxhoorn","year":"2020","journal-title":"Lancet"},{"key":"2023032107474401600_","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/den.13470","article-title":"Superiority of endoscopic interventions over minimally invasive surgery for infected necrotizing pancreatitis: meta-analysis of randomized trials","volume":"32","author":"Bang","year":"2020","journal-title":"Dig Endosc"},{"key":"2023032107474401600_","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.pan.2020.10.044","article-title":"Experimental pancreatitis is characterized by rapid T cell activation, Th2 differentiation that parallels disease severity, and improvement after CD4(+) T cell 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