Cargando…

Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages

Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macropha...

Descripción completa

Detalles Bibliográficos
Autores principales: Ke, Ping, Shao, Bo-Zong, Xu, Zhe-Qi, Wei, Wei, Han, Bin-Ze, Chen, Xiong-Wen, Su, Ding-Feng, Liu, Chong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017608/
https://www.ncbi.nlm.nih.gov/pubmed/27611972
http://dx.doi.org/10.1371/journal.pone.0155076
_version_ 1782452779720114176
author Ke, Ping
Shao, Bo-Zong
Xu, Zhe-Qi
Wei, Wei
Han, Bin-Ze
Chen, Xiong-Wen
Su, Ding-Feng
Liu, Chong
author_facet Ke, Ping
Shao, Bo-Zong
Xu, Zhe-Qi
Wei, Wei
Han, Bin-Ze
Chen, Xiong-Wen
Su, Ding-Feng
Liu, Chong
author_sort Ke, Ping
collection PubMed
description Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1). Pretreatment of peritoneal macrophages with HU 308, a selective CB2R agonist, attenuated LPS/DSS-induced NLRP3 inflammasome activation, but further enhanced autophagy. In comparison with wild-type (WT) control, peritoneal macrophages from CB2R knockout (KO) mice had more robust NLRP3 inflammasome activation and attenuated autophagy upon LPS/DSS challenge. Knockdown autophagy-related gene 5 (Atg5) with a siRNA in peritoneal macrophages attenuated the inhibitory effects of HU 308 on LPS/DSS-induced NLRP3 inflammasome activation in vitro. In vivo, HU308 treatment attenuated DSS-induced colitis mice associated with reduced colon inflammation and inhibited NLRP3 inflammasome activation in wild-type mice. In CB2R KO mice, DSS-induced inflammation and NLRP3 inflammasome activation were more pronounced than those in WT control. Finally, we demonstrated that AMPK-mTOR-P70S6K signaling pathway was involved in this CB2R-mediated process. We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.
format Online
Article
Text
id pubmed-5017608
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-50176082016-09-27 Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages Ke, Ping Shao, Bo-Zong Xu, Zhe-Qi Wei, Wei Han, Bin-Ze Chen, Xiong-Wen Su, Ding-Feng Liu, Chong PLoS One Research Article Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1). Pretreatment of peritoneal macrophages with HU 308, a selective CB2R agonist, attenuated LPS/DSS-induced NLRP3 inflammasome activation, but further enhanced autophagy. In comparison with wild-type (WT) control, peritoneal macrophages from CB2R knockout (KO) mice had more robust NLRP3 inflammasome activation and attenuated autophagy upon LPS/DSS challenge. Knockdown autophagy-related gene 5 (Atg5) with a siRNA in peritoneal macrophages attenuated the inhibitory effects of HU 308 on LPS/DSS-induced NLRP3 inflammasome activation in vitro. In vivo, HU308 treatment attenuated DSS-induced colitis mice associated with reduced colon inflammation and inhibited NLRP3 inflammasome activation in wild-type mice. In CB2R KO mice, DSS-induced inflammation and NLRP3 inflammasome activation were more pronounced than those in WT control. Finally, we demonstrated that AMPK-mTOR-P70S6K signaling pathway was involved in this CB2R-mediated process. We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages. Public Library of Science 2016-09-09 /pmc/articles/PMC5017608/ /pubmed/27611972 http://dx.doi.org/10.1371/journal.pone.0155076 Text en © 2016 Ke et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ke, Ping
Shao, Bo-Zong
Xu, Zhe-Qi
Wei, Wei
Han, Bin-Ze
Chen, Xiong-Wen
Su, Ding-Feng
Liu, Chong
Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title_full Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title_fullStr Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title_full_unstemmed Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title_short Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages
title_sort activation of cannabinoid receptor 2 ameliorates dss-induced colitis through inhibiting nlrp3 inflammasome in macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017608/
https://www.ncbi.nlm.nih.gov/pubmed/27611972
http://dx.doi.org/10.1371/journal.pone.0155076
work_keys_str_mv AT keping activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT shaobozong activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT xuzheqi activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT weiwei activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT hanbinze activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT chenxiongwen activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT sudingfeng activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages
AT liuchong activationofcannabinoidreceptor2amelioratesdssinducedcolitisthroughinhibitingnlrp3inflammasomeinmacrophages