2016年9月
Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome
SCIENTIFIC REPORTS
- 巻
- 6
- 号
- 開始ページ
- 32587
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/srep32587
- 出版者・発行元
- NATURE PUBLISHING GROUP
The inflammasome is a large, multiprotein complex that consists of a nucleotide-binding oligomerization domain-like receptor (NLR), an apoptosis-associated speck-like protein containing a caspase recruitment domain, and pro-caspase-1. Activation of the inflammasome results in cleavage of pro-caspase-1 into cleaved caspase-1, which promotes the processing of pro-interleukin (IL)-1 beta into mature IL-1 beta. We investigated the effects of colchicine on non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury and activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Colchicine treatment inhibited indomethacin-induced small intestinal injury by 86% (1 mg/kg) and 94% (3 mg/kg) as indicated by the lesion index 24 h after indomethacin administration. Colchicine inhibited the protein expression of cleaved caspase-1 and mature IL-1 beta, without affecting the mRNA expression of NLRP3 and IL-1 beta. Although treatment with recombinant IL-1 beta (0.1 mu g/kg) did not change the severity of small intestinal damage, the preventive effects of colchicine were abolished by supplementation with the same dose of recombinant IL-1 beta. Indomethacin-induced small intestinal damage was reduced by 77%, as determined by the lesion index in NLRP3(-/-) mice, and colchicine treatment failed to inhibit small intestinal damage in NLRP3(-/-) mice. These results demonstrate that colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome.
- リンク情報
- ID情報
-
- DOI : 10.1038/srep32587
- ISSN : 2045-2322
- PubMed ID : 27585971
- Web of Science ID : WOS:000382475300002