Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome.
Sci Rep
; 6: 32587, 2016 09 02.
Article
em En
| MEDLINE
| ID: mdl-27585971
ABSTRACT
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)-1ß into mature IL-1ß. 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-1ß, without affecting the mRNA expression of NLRP3 and IL-1ß. Although treatment with recombinant IL-1ß (0.1 µg/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-1ß. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
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Colchicina
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Intestino Delgado
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article