Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome

被引：58

作者：

Otani, Koji ^{[1
]}

Watanabe, Toshio ^{[1
]}

Shimada, Sunao ^{[1
]}

Takeda, Shogo ^{[1
]}

Itani, Shigehiro ^{[1
]}

Higashimori, Akira ^{[1
]}

Nadatani, Yuji ^{[1
]}

Nagami, Yasuaki ^{[1
]}

Tanaka, Fumio ^{[1
]}

Kamata, Noriko ^{[1
]}

Yamagami, Hirokazu ^{[1
]}

Tanigawa, Tetsuya ^{[1
]}

Shiba, Masatsugu ^{[1
]}

Tominaga, Kazunari ^{[1
]}

Fujiwara, Yasuhiro ^{[1
]}

Arakawa, Tetsuo ^{[1
]}

机构：

[1] Osaka City Univ, Grad Sch Med, Dept Gastroenterol, Abeno Ku, 1-4-3 Asahimachi, Osaka, Japan

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

SMALL-BOWEL INJURY; GENERALIZED PUSTULAR PSORIASIS; CAPSULE ENDOSCOPY; RHEUMATOID-ARTHRITIS; NALP3; INFLAMMASOME; RISK-FACTORS; MECHANISMS; DAMAGE; CYCLOOXYGENASE; CRYSTALS;

D O I：

10.1038/srep32587

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 46 条

[1] NALP3 forms an IL-lβ-Processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J].