{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:51:53Z","timestamp":1771530713119,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1124,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory\/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Only the myocytes\u2010containing explants produced tumor necrosis factor alpha (TNF<jats:italic>\u03b1<\/jats:italic>), <jats:italic>via<\/jats:italic> an ADAM17 (a disintegrin and metalloproteinase\u201017)\u2010dependent pathway, as shown by the abrogation of TNF<jats:italic>\u03b1<\/jats:italic> production by the inhibitor Tapi\u20102. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNF<jats:italic>\u03b1<\/jats:italic> and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time\u2010course experiments on explanted tissues showed that TNF<jats:italic>\u03b1<\/jats:italic> production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, this study identifies human intestinal myocytes as resident cells able to initiate an inflammatory reaction through TNF<jats:italic>\u03b1<\/jats:italic> production in postischemic conditions, and delineates two points of control in TNF<jats:italic>\u03b1<\/jats:italic> production, NF\u2010<jats:italic>\u03ba<\/jats:italic>B and ADAM17, which can be targeted by pharmacological manipulation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2006) <jats:bold>147<\/jats:bold>, 64\u201372. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706449\">10.1038\/sj.bjp.0706449<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706449","type":"journal-article","created":{"date-parts":[[2005,11,7]],"date-time":"2005-11-07T04:17:37Z","timestamp":1131337057000},"page":"64-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Human colonic myocytes are involved in postischemic inflammation through ADAM17\u2010dependent TNF<i>\u03b1<\/i> production"],"prefix":"10.1111","volume":"147","author":[{"given":"Anne","family":"Jarry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyane","family":"Bach\u2010Ngohou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damien","family":"Masson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dejoie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul\u2010Antoine","family":"Lehur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Mosnier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc G","family":"Denis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian L","family":"Laboisse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(99)70209-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.10.5678"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/385729a0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1814"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00139-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.4.1498"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5240"},{"key":"e_1_2_7_9_1","first-page":"795","volume-title":"Gastrointestinal Pathology. 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