{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:05:09Z","timestamp":1792782309103,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2017-01621"],"award-info":[{"award-number":["2017-01621"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Einar and Inga Nilsson Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent evidence suggests that neutrophil extracellular traps (NETs) play an important role in the development of acute pancreatitis (AP). Herein, we examined the role of peptidylarginine deiminase (PAD), which has been shown to regulate NET formation, in severe AP. AP was induced by retrograde of taurocholate infusion into pancreatic duct in C57BL\/6 mice. PAD was pharmacologically inhibited using Cl\u2010amidine, a pan\u2010PAD inhibitor. Pancreata were collected, and histones, citrullinated histone 3, chemokines, myeloperoxidase, and NETs were quantified. Chemokines, matrix metalloproteinase\u20109 (MMP\u20109), interleukin\u20106 (IL\u20106), and DNA\u2010histone complexes were determined in plasma samples. Infusion of taurocholate induced formation of NETs in pancreatic tissues of mice. Pretreatment with Cl\u2010amidine markedly reduced the NET formation in the inflamed pancreas. Moreover, inhibition of PAD decreased the levels of blood amylase as well as edema, acinar cell necrosis, hemorrhage, and neutrophil infiltration in the pancreas of animals with AP. Administration of Cl\u2010amidine attenuated the myeloperoxidase levels in the pancreas and lung of mice exposed to taurocholate. In addition, Cl\u2010amidine decreased pancreatic levels of CXC chemokines, plasma levels of IL\u20106, and MMP\u20109 in mice with severe AP. This study shows that Cl\u2010amidine is a potent inhibitor of NET formation in severe AP. Also, our results suggest that PAD regulates pathological inflammation and tissue damage in the inflamed pancreas. Thus, targeting PAD might be a useful strategy to treat patients with severe AP.<\/jats:p>","DOI":"10.1002\/jcp.27874","type":"journal-article","created":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T23:42:56Z","timestamp":1543966976000},"page":"11850-11860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis"],"prefix":"10.1002","volume":"234","author":[{"given":"Raed","family":"Madhi","sequence":"first","affiliation":[{"name":"Department of Surgery, Clinical Sciences, Malm\u00f6 Sk\u00e5ne University Hospital, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-4848","authenticated-orcid":false,"given":"Milladur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinical Sciences, Malm\u00f6 Sk\u00e5ne University Hospital, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dler","family":"Taha","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinical Sciences, Malm\u00f6 Sk\u00e5ne University Hospital, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"M\u00f6rgelin*","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinical Sciences, Malm\u00f6 Sk\u00e5ne University Hospital, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7827-996X","authenticated-orcid":false,"given":"Henrik","family":"Thorlacius","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinical Sciences, Malm\u00f6 Sk\u00e5ne University Hospital, Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0411195"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb799"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0811443"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01225.x"},{"issue":"2","key":"e_1_2_7_1_6_1","first-page":"167","article-title":"Chemokines in disease models and pathogenesis","volume":"9","author":"Bacon K. B.","year":"1998","journal-title":"Cytokine and Growth Factor Reviews"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2006.08.006"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202671"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2008985"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00435.2010"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70192-7"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00243.2014"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.7775"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022043"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201719"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303312"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67390"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.124230"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10973"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1735"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100239"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603297"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00365.2013"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi061180d"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-587709"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.02.002"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.08.026"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010520"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000675"},{"key":"e_1_2_7_1_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70077-X"},{"key":"e_1_2_7_1_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199201000-00007"},{"key":"e_1_2_7_1_33_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.95.08060954"},{"key":"e_1_2_7_1_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10357"},{"key":"e_1_2_7_1_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806072"},{"key":"e_1_2_7_1_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22156-5"},{"key":"e_1_2_7_1_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101400"},{"key":"e_1_2_7_1_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001620"},{"issue":"4","key":"e_1_2_7_1_39_1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.pan.2013.07.063","article-title":"IAP\/APA evidence\u2010based guidelines for the management of acute pancreatitis","volume":"13","year":"2013","journal-title":"Pancreatology"},{"key":"e_1_2_7_1_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64931"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.27874","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27874","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.27874","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.27874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T15:21:15Z","timestamp":1692976875000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.27874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,4]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/jcp.27874"],"URL":"https:\/\/doi.org\/10.1002\/jcp.27874","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,4]]},"assertion":[{"value":"2018-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}