Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1ß production.
Mol Immunol
; 104: 11-19, 2018 12.
Article
de En
| MEDLINE
| ID: mdl-30396035
ABSTRACT
BACKGROUND:
NLRP3 inflammasome mediates IL-1ß maturation, therefore plays a vital role in the development of IBD. Curcumin is known for possessing strong anti-inflammatory property.OBJECTIVE:
The present study was to investigate the protective effects of curcumin on dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome activation and IL-1ß production.METHODS:
LPS-primed macrophages were treated with curcumin prior to DSS triggering NLRP3 inflammasome activation, IL-1ß secretion and ASC oligomerization were observed. The mechanisms of curcumin in the inhibition of DSS-induced inflammasome activation were explored. Curcumin or caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitis mouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1ß and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitis severity.RESULTS:
NLRP3 inflammasome activation was dramatically inhibited by curcumin in DSS-stimulated macrophages, as evidenced by decreased IL-1ß secretion, less caspase-1 activation and ASC specks. Mechanistically, curcumin prevented DSS-induced K+ efflux, intracellular ROS formation and cathepsin B release, three major cellular events mediating NLRP3 inflammasome activation. In DSS-induced colitis, curcumin administration significantly ameliorated colitis symptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcumin significantly decreased the expression of multiple inflammatory cytokines (including mature IL-1ß, IL-6, MCP-1), MPO activity, caspase-1 activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasome activation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcumin on DSS-induced colitis.CONCLUSION:
Curcumin could strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSS-induced colitis in mice, thus it may be a promising candidate drug in clinical application for IBD therapy.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Sulfate dextran
/
Colite
/
Curcumine
/
Interleukine-1 bêta
/
Inflammasomes
/
Protéine-3 de la famille des NLR contenant un domaine pyrine
Limites:
Animals
Langue:
En
Journal:
Mol Immunol
Année:
2018
Type de document:
Article