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Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome
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Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome
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Journal Article
Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome
2016
Overview
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)-1β into mature IL-1β. 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-1β, without affecting the mRNA expression of NLRP3 and IL-1β. Although treatment with recombinant IL-1β (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-1β. 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.
Publisher
Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group
Subject
/ 82/51
/ 82/80
/ Animals
/ Anti-Inflammatory Agents, Non-Steroidal
/ Anti-Inflammatory Agents, Non-Steroidal - adverse effects
/ Caspase
/ Humanities and Social Sciences
/ IL-1β
/ Indomethacin - administration & dosage
/ Indomethacin - adverse effects
/ Interleukin-1beta - pharmacology
/ Intestine, Small - drug effects
/ Intestine, Small - enzymology
/ Intestine, Small - pathology
/ Lesions
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Nonsteroidal anti-inflammatory drugs
/ Rodents
/ Science
