{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:22:31Z","timestamp":1776846151378,"version":"3.51.2"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T00:00:00Z","timestamp":1110499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytokines play a critical role in acute pancreatitis (AP) but the contribution of different cell sources to cytokine production is unclear. Unfortunately, there are no data concerning the molecular mechanisms involved in the inflammatory response in humans during AP. For this reason, the aim of this study was to analyse the ability of acinar cells, in comparison with leukocytes, to produce TNF\u2010\u03b1 at different stages of AP induced in rats by bile\u2013pancreatic duct obstruction (BPDO) and to investigate the time course of oxidant\u2010sensitive mechanisms involved in cytokine production. The role of oxygen free radicals as messengers of the mechanisms underlying acinar cell TNF\u2010\u03b1 production was assessed in BPDO rats treated with <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC). While monocytes were not able to produce TNF\u2010\u03b1 until 12 h after inducing AP, acinar cells triggered TNF\u2010\u03b1 production from 6 h after BPDO, at which time the pancreas develops maximal oxidative stress. Phosphorylated p38\u2010MAPK and activated NF\u2010\u03baB were detected in acinar cells from 6 h after BPDO. NAC treatment reduced pancreatic glutathione depletion during the early stages of AP and attenuated the activation of p38\u2010MAPK and NF\u2010\u03baB for 48 h following BPDO. As a result, acinar cells in NAC\u2010treated rats failed to produce TNF\u2010\u03b1 during AP. In addition, NAC delayed monocyte TNF\u2010\u03b1 production, thereby maintaining low TNF\u2010\u03b1 levels in plasma during BPDO. In conclusion, acinar cells contribute directly to the inflammatory response during BPDO\u2010induced AP by producing TNF\u2010\u03b1 even before inflammatory cells in the peripheral blood. The blockade of oxidant\u2010mediated signal transduction pathways induced by NAC treatment prevented acinar cell TNF\u2010\u03b1 production. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1747","type":"journal-article","created":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T06:46:21Z","timestamp":1110523581000},"page":"9-16","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Kinetic study of TNF\u2010\u03b1 production and its regulatory mechanisms in acinar cells during acute pancreatitis induced by bile\u2013pancreatic duct obstruction"],"prefix":"10.1002","volume":"206","author":[{"given":"Laura","family":"Ramudo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel A","family":"Manso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Sevillano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"de Dios","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,3,11]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365529109025030"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114995"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02798921"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00031x.2002"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000032377.09626.C7"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119714"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.6.G1197"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1995.01430090052018"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.6.G1402"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.31060"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050078"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81694-3"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(96)00501-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(94)34085-4"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.10.7.8635688"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-200011000-00008"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.807"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1091-255X(02)00053-7"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5257"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70140-X"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000077067"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v7.i2.259"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.6.C1993"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000129343.47774.89"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01470-2"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(02)00160-6"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60985-0"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1970.sp009013"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(69)90064-5"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.2011"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(96)00249-5"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(97)00240-7"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2004.00372.x"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198410000-00003"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(01)00247-9"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1159\/000200487"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(97)00271-2"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3130017"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.10.110194.002201"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.11.5264"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2003.09.003"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8355"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1747","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1747","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:29:10Z","timestamp":1761053350000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,11]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1002\/path.1747"],"URL":"https:\/\/doi.org\/10.1002\/path.1747","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,11]]},"assertion":[{"value":"2004-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-12-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}