{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:43:42Z","timestamp":1761093822357,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Helsinki University Hospital Special Funds"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epithelial cell injury, inflammation, progressive fibrosis, and airway obliteration are histological features of post\u2010transplant obliterative bronchiolitis (OB). Cyclooxygenase (COX)\u20102 is expressed in acute and chronic inflammatory responses. Our aim was to elucidate the possible role of COX\u20102 in post\u2010transplant OB by using a heterotopic bronchial porcine model. Bronchial allografts from non\u2010related donors were transplanted subcutaneously into 24 random\u2010bred domestic pigs, each weighing about 20 kg. Groups studied had grafts, non\u2010treated allografts, allografts given cyclosporine A (CsA), methylprednisolone (MP), and azathioprine (Aza), and allografts given CsA, MP, and everolimus. Grafts were serially harvested during a follow\u2010up period of 21 days for histology (H&amp;E) and immunohistochemistry. Immunostaining was performed with monoclonal IgG against human COX\u20102 peptide, and histological alterations and immunohistochemical positivity were graded on a scale from 0 to 5. Epithelial COX\u20102 index was calculated by multiplying the percentage of positive cells by grade of epithelial COX\u20102 intensity. Ischaemic epithelial loss, evident in all implants, recovered rapidly in autografts, and bronchi remained patent. Epithelial loss in non\u2010treated allografts preceded fibroblast proliferation, resulting in total luminal obliteration. In CsA\u2010, MP\u2010, and Aza\u2010treated allografts epithelial destruction and luminal obliteration were delayed, and these were prevented in CsA\u2010, MP\u2010, and everolimus\u2010treated allografts. COX\u20102 expression due to operative ischaemia was evident in all implants on day 2. Thereafter, the epithelial COX\u20102 index preceded epithelial injury and obliteration. During the inflammatory response and fibroblast proliferation, COX\u20102 expression occurred in macrophages and fibroblasts. In conclusion, in the early stage of OB development, COX\u20102 induction occurred in airway epithelial cells prior to luminal obliteration. In addition, the observation that COX\u20102 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation indicates a role in OB development, but the causal relationships need further study. Copyright \u00a9 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1631","type":"journal-article","created":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T13:02:03Z","timestamp":1097240523000},"page":"340-348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cyclooxygenase\u20102 expression in experimental post\u2010transplant obliterative bronchiolitis"],"prefix":"10.1002","volume":"204","author":[{"given":"Outi E","family":"P\u00e4iv\u00e4niemi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula K","family":"Maasilta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanni S","family":"Alho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Henrik J","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla\u2010Stina","family":"Salminen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(03)00182-7"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(02)00398-4"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.5.1411"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3062.2001.003003168.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)00212-X"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2044.2000.01271.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.5.2441"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.56.5.351"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090000094"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.13e12.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.4.430"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(99)00118-7"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199910150-00012"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200208270-00022"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200002270-00031"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200109270-00004"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.601"},{"key":"e_1_2_6_19_2","first-page":"4997","article-title":"Expression of cyclooxygenase\u20102 in human lung carcinoma","volume":"58","author":"Wolff H","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2000.014s1064.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf125"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-200202000-00003"},{"key":"e_1_2_6_23_2","first-page":"3761","article-title":"Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas","volume":"58","author":"Hida T","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200005000-00008"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(00)00047-1"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-4975(95)00776-8"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.3.646"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200206150-00006"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200212150-00009"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000085211.97972.2C"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34174-7"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.102.3.832"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1631","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1631","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:12:02Z","timestamp":1761052322000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1631"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,8]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["10.1002\/path.1631"],"URL":"https:\/\/doi.org\/10.1002\/path.1631","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"type":"print","value":"0022-3417"},{"type":"electronic","value":"1096-9896"}],"subject":[],"published":{"date-parts":[[2004,10,8]]},"assertion":[{"value":"2004-02-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}