Abstract | BACKGROUND: AIMS: To investigate role of TLR4 in inflammatory responses in indomethacin-induced enteropathy. METHODS: RESULTS:
Indomethacin induced small intestinal damage with an increase in expression of TNF-alpha and MCP-1 in both rats and mice. Antibodies against neutrophils, TNF-alpha and MCP-1 inhibited the damage by 83%, 67% and 63%, respectively, in rats. Ampicillin and aztreonam also inhibited this damage, and decreased the number of Gram-negative bacteria in the small intestinal contents of the rat. However, vancomycin, which exhibited no activity against Gram-negative bacteria, had no preventive effect against this damage. Administration of LPS 1 h after indomethacin aggravated the damage, whereas LPS pretreatment inhibited it with reduction of expression of TLR4 and cytokines. In TLR4-mutant mice, the damage and cytokine expression were markedly inhibited. TLR4(-/-) and MyD88(-/-) mice were also resistant to the damage. CONCLUSIONS:
Indomethacin may injure the small intestine through a TLR4/MyD88-dependent pathway.
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Authors | T Watanabe, K Higuchi, A Kobata, H Nishio, T Tanigawa, M Shiba, K Tominaga, Y Fujiwara, N Oshitani, T Asahara, K Nomoto, K Takeuchi, T Arakawa |
Journal | Gut
(Gut)
Vol. 57
Issue 2
Pg. 181-7
(Feb 2008)
ISSN: 1468-3288 [Electronic] England |
PMID | 17639086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Lipopolysaccharides
- Myeloid Differentiation Factor 88
- TLR4 protein, human
- Toll-Like Receptor 4
- Tumor Necrosis Factor-alpha
- Indomethacin
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects)
- Blotting, Western
- Indomethacin
(adverse effects)
- Intestinal Diseases
(chemically induced)
- Intestine, Small
(drug effects)
- Lipopolysaccharides
(antagonists & inhibitors)
- Mice
- Myeloid Differentiation Factor 88
(antagonists & inhibitors)
- Rats
- Reverse Transcriptase Polymerase Chain Reaction
- Toll-Like Receptor 4
(physiology)
- Tumor Necrosis Factor-alpha
(metabolism)
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