Source:http://linkedlifedata.com/resource/pubmed/id/19101538
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-3
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pubmed:dateCreated |
2009-1-26
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pubmed:abstractText |
A number of clinical studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) exacerbate inflammatory bowel disease; however the molecular mechanism whereby this occurs remains unclear. NSAIDs inhibit cyclooxygenase (COX), which has subtypes COX-1 and COX-2. In this study, we have examined the effect of various types of NSAIDs on the development of dextran sulfate sodium (DSS)-induced colitis, an animal model of inflammatory bowel disease. The DSS-induced colitis was worsened by administration of non-selective NSAIDs but not by COX-1 or COX-2 selective inhibitors. However, administration of a combination of both COX-1- and COX-2-selective inhibitors exacerbated the colitis. The intestinal level of PGE(2) dramatically decreased in response to administration of COX-1- and COX-2-selective inhibitors, and exogenously administered PGE(2) suppressed the exacerbation of colitis by NSAIDs. The expression of mucin proteins, which protect the intestinal mucosa, was suppressed by non-selective NSAIDs and this expression was restored by PGE(2), both in vivo and in vitro. Intestinal mucosal cell growth was inhibited by non-selective NSAIDs and this cell growth was restored by PGE(2), both in vivo and in vitro. This study provides evidence that inhibition of both COX-1 and COX-2 and the resulting dramatic decrease in the intestinal level of PGE(2) is responsible for NSAID-dependent exacerbation of DSS-induced colitis. Furthermore, expression of mucin proteins and intestinal mucosal cell growth seems to be involved in this exacerbation and its suppression by PGE(2).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Dextran Sulfate,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Mucins,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1879-0712
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
603
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
120-32
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pubmed:meshHeading |
pubmed-meshheading:19101538-Animals,
pubmed-meshheading:19101538-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:19101538-Apoptosis,
pubmed-meshheading:19101538-Cell Line,
pubmed-meshheading:19101538-Cell Proliferation,
pubmed-meshheading:19101538-Colitis,
pubmed-meshheading:19101538-Cyclooxygenase 1,
pubmed-meshheading:19101538-Cyclooxygenase 2,
pubmed-meshheading:19101538-Cyclooxygenase Inhibitors,
pubmed-meshheading:19101538-Cytokines,
pubmed-meshheading:19101538-Dextran Sulfate,
pubmed-meshheading:19101538-Dinoprostone,
pubmed-meshheading:19101538-Epithelial Cells,
pubmed-meshheading:19101538-Gene Expression Regulation,
pubmed-meshheading:19101538-Intestinal Mucosa,
pubmed-meshheading:19101538-Mucins,
pubmed-meshheading:19101538-Reactive Oxygen Species
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pubmed:year |
2009
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pubmed:articleTitle |
Inhibition of both COX-1 and COX-2 and resulting decrease in the level of prostaglandins E2 is responsible for non-steroidal anti-inflammatory drug (NSAID)-dependent exacerbation of colitis.
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pubmed:affiliation |
Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
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pubmed:publicationType |
Journal Article
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