{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:40:28Z","timestamp":1778841628798,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2001,9,1]],"date-time":"2001-09-01T00:00:00Z","timestamp":999302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipoxins (LXs) are lipoxygenase-derived eicosanoids and putative endogenous braking signals for inflammation in the gastrointestinal tract and other organs. Aspirin triggers the production of 15-epimers during cell-cell interaction in a cytokine-primed milieu, and aspirin-triggered 15-epi-5(S),6(R),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi-LXA4) may contribute to the bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in vivo. We determined the effect of LXA4, 15-(R\/S)-methyl-11,12-dehydro-LXA4 methyl ester (15-(R\/S)-methyl-LXA4), and stable analogs of LXA4 on TNF-\u03b1-stimulated neutrophil-enterocyte interaction in vitro and TNF-\u03b1-stimulated chemokine release, changes in mucosal architecture, and enterocyte apoptosis in cytokine-activated intact human colonic mucosa ex vivo. LXA4, 15-(R\/S)-epi-LXA4, and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA4 methyl ester (16-phenoxy-LXA4) inhibited TNF-\u03b1-stimulated neutrophil adherence to epithelial monolayers at nanomolar concentrations. In parallel experiments involving human colonic mucosa ex vivo, LXA4potently attenuated TNF-\u03b1-stimulated release of the C-X-C chemokine IL-8, and the C-C chemokines monocyte-chemoattractant protein-1 (MCP-1) and RANTES. Exposure of strips of normal human colonic mucosa to TNF-\u03b1 induced disruption of mucosa architecture and enhanced colonocyte apoptosis via a caspase-3-independent mechanism. Prior exposure of the mucosa strips to 15-(R\/S)-methyl-LXA4 attenuated TNF-\u03b1-stimulated colonocyte apoptosis and protected the mucosa against TNF-\u03b1-induced mucosal damage. In aggregate, our data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA4 are potent antagonists of TNF-\u03b1-mediated neutrophil-enterocyte interactions in vitro, attenuate TNF-\u03b1-triggered chemokine release and colonocyte apoptosis, and are protective against TNF-\u03b1-induced morphological disruption in human colonic strips ex vivo. Our observations further expand the anti-inflammatory profile of these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for the treatment of inflammatory bowel disease.<\/jats:p>","DOI":"10.4049\/jimmunol.167.5.2772","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:43:49Z","timestamp":1398023029000},"page":"2772-2780","source":"Crossref","is-referenced-by-count":56,"title":["Lipoxin A4 and Aspirin-Triggered 15-Epi-Lipoxin A4 Antagonize TNF-\u03b1-Stimulated Neutrophil-Enterocyte Interactions In Vitro and Attenuate TNF-\u03b1-Induced Chemokine Release and Colonocyte Apoptosis in Human Intestinal Mucosa Ex Vivo"],"prefix":"10.1093","volume":"167","author":[{"given":"Jason","family":"Goh","sequence":"first","affiliation":[{"name":"Gastroenterology, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan W","family":"Baird","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conor","family":"O\u2019Keane","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R William G","family":"Watson","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cottell","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California , Los Angeles, CA 90089"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicos A","family":"Petasis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California , Los Angeles, CA 90089"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Godson","sequence":"additional","affiliation":[{"name":"Medicine and Therapeutics, Mater Misericordiae Hospital, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]},{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh R","family":"Brady","sequence":"additional","affiliation":[{"name":"Medicine and Therapeutics, Mater Misericordiae Hospital, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]},{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padraic","family":"MacMathuna","sequence":"additional","affiliation":[{"name":"Gastroenterology, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]},{"name":"Conway Institute of Biomolecular and Biomedical Research, University College Dublin, and the Dublin Molecular Medicine Centre , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,9,1]]},"reference":[{"key":"2026020208045072200_R1","first-page":"603","volume-title":"Gut","year":"1998"},{"key":"2026020208045072200_R2","first-page":"57","volume-title":"Alimen. 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