論文 - 詳細
| RRC ID | 37793 |
|---|---|
| 著者 | Tanaka K, Suemasu S, Ishihara T, Tasaka Y, Arai Y, Mizushima T. |
| タイトル | 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. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
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). |
| 巻・号 | 603(1-3) |
| ページ | 120-32 |
| 公開日 | 2009-1-28 |
| DOI | 10.1016/j.ejphar.2008.11.058 |
| PII | S0014-2999(08)01212-0 |
| PMID | 19101538 |
| MeSH | Animals Anti-Inflammatory Agents, Non-Steroidal / adverse effects* Apoptosis / drug effects Cell Line Cell Proliferation / drug effects Colitis / chemically induced* Colitis / enzymology Colitis / metabolism* Colitis / pathology Cyclooxygenase 1 / metabolism* Cyclooxygenase 2 / metabolism* Cyclooxygenase Inhibitors / pharmacology* Cytokines / metabolism Dextran Sulfate / toxicity Dinoprostone / metabolism* Dinoprostone / pharmacology Epithelial Cells / drug effects Epithelial Cells / metabolism Epithelial Cells / pathology Gene Expression Regulation / drug effects Intestinal Mucosa / drug effects Intestinal Mucosa / pathology Mucins / metabolism Reactive Oxygen Species / metabolism |
| IF | 3.263 |
| 引用数 | 39 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |