Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Cannabinoid-induced autophagy regulates suppressor of cytokine signaling (SOCS)-3 in intestinal epithelium
AU - Koay, Luan
AU - Rigby, Rachael
AU - Wright, Karen
PY - 2014/7/15
Y1 - 2014/7/15
N2 - Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associates impaired autophagy, increased activity in the endocannabinoid system and upregulation of suppressor of cytokine signaling (SOCS)-3 protein expression during intestinal inflammatory states. We have investigated whether these three processes are linked. By assessing the impact of phyto-cannabinoid cannabidiol (CBD), synthetic cannabinoid (ACEA) and endocannabinoid (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated CaCo2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid receptor (CB)-1 mediated. In contrast, CBD was able to bypass both the CB1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking both early and late autophagy. In conclusion, the regulatory protein, SOCS3, is itself regulated by autophagy and cannabinoids play a role in this process, which could be important when considering therapeutic applications for the cannabinoids in inflammatory conditions.
AB - Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associates impaired autophagy, increased activity in the endocannabinoid system and upregulation of suppressor of cytokine signaling (SOCS)-3 protein expression during intestinal inflammatory states. We have investigated whether these three processes are linked. By assessing the impact of phyto-cannabinoid cannabidiol (CBD), synthetic cannabinoid (ACEA) and endocannabinoid (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated CaCo2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid receptor (CB)-1 mediated. In contrast, CBD was able to bypass both the CB1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking both early and late autophagy. In conclusion, the regulatory protein, SOCS3, is itself regulated by autophagy and cannabinoids play a role in this process, which could be important when considering therapeutic applications for the cannabinoids in inflammatory conditions.
KW - cannabinoid
KW - SOCS3
KW - Autophagy
U2 - 10.1152/ajpgi.00317.2013
DO - 10.1152/ajpgi.00317.2013
M3 - Journal article
VL - 307
SP - G140-G148
JO - American Journal of Physiology-Gastrointestinal and Liver Physiology
JF - American Journal of Physiology-Gastrointestinal and Liver Physiology
SN - 0193-1857
ER -