Source:http://linkedlifedata.com/resource/pubmed/id/11509622
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rdf:type | |
lifeskim:mentions |
umls-concept:C0021839,
umls-concept:C0030685,
umls-concept:C0086418,
umls-concept:C0162638,
umls-concept:C0282554,
umls-concept:C0391871,
umls-concept:C0599689,
umls-concept:C0599946,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1533691,
umls-concept:C1704675,
umls-concept:C1963578,
umls-concept:C2348480
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pubmed:issue |
5
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pubmed:dateCreated |
2001-8-17
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pubmed:abstractText |
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-LXA(4)) may contribute to the bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in vivo. We determined the effect of LXA(4), 15-(R/S)-methyl-11,12-dehydro-LXA(4) methyl ester (15-(R/S)-methyl-LXA(4)), and stable analogs of LXA(4) on TNF-alpha-stimulated neutrophil-enterocyte interaction in vitro and TNF-alpha-stimulated chemokine release, changes in mucosal architecture, and enterocyte apoptosis in cytokine-activated intact human colonic mucosa ex vivo. LXA(4), 15-(R/S)-epi-LXA(4), and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA(4) methyl ester (16-phenoxy-LXA(4)) inhibited TNF-alpha-stimulated neutrophil adherence to epithelial monolayers at nanomolar concentrations. In parallel experiments involving human colonic mucosa ex vivo, LXA(4)potently attenuated TNF-alpha-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-alpha 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-LXA(4) attenuated TNF-alpha-stimulated colonocyte apoptosis and protected the mucosa against TNF-alpha-induced mucosal damage. In aggregate, our data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA(4) are potent antagonists of TNF-alpha-mediated neutrophil-enterocyte interactions in vitro, attenuate TNF-alpha-triggered chemokine release and colonocyte apoptosis, and are protective against TNF-alpha-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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Aspirin,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/lipoxin A4
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2772-80
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11509622-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11509622-Apoptosis,
pubmed-meshheading:11509622-Aspirin,
pubmed-meshheading:11509622-Cell Line,
pubmed-meshheading:11509622-Chemokine CCL2,
pubmed-meshheading:11509622-Chemokine CCL5,
pubmed-meshheading:11509622-Chemokines,
pubmed-meshheading:11509622-Enterocytes,
pubmed-meshheading:11509622-Humans,
pubmed-meshheading:11509622-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:11509622-Interleukin-8,
pubmed-meshheading:11509622-Intestinal Mucosa,
pubmed-meshheading:11509622-Lipoxins,
pubmed-meshheading:11509622-Microscopy, Electron,
pubmed-meshheading:11509622-Neutrophils,
pubmed-meshheading:11509622-Tumor Necrosis Factor-alpha
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pubmed:year |
2001
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pubmed:articleTitle |
Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo.
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pubmed:affiliation |
Department of Gastroenterology, Mater Misericordiae Hospital, Dublin, Ireland.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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