ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL RESOLVING NEUROINFLAMMATION IS MEDIATED BY PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-y
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
Emerging information suggests that endocannabinoids display anti-inflammatory and neuroprotective properties. However, the mechanisms responsible for endocannabinoids in resolving neuroinflammation are largely unknown. We previously demonstrated that 2arachidonoylglycerol (2-AG) protects hippocampal neurons by limiting inflammatory cyclooxygenase-2 (COX-2) expression via a CB1 receptor-dependent MAPK/NF-KB signaling pathway. Here, we show that exogenous and endogenous 2-AG-produced suppressions of NFKB phosphorylation, COX-2 expression and excitatory synaptic transmission in response to proinflammatory interleukin-1 ~ (IL-1 ~) and lipopolysaccharide (LPS) were inhibited by GW9662, a selective peroxisome proliferator-activated receptor-y (PPARy) antagonist, in hippocampal neurons in culture. PPARy agonists 15-deoxy-Ll12'14-prostaglandin J2 (15d-PGJ2) and rosiglitazone mimicked the effects of 2-AG on NF-KB phosphorylation, COX-2 expression and excitatory synaptic transmission, and the effects were eliminated by antagonism of PPARy. Moreover, exogenous application of 2-AG or elevation of endogenous 2-AG by inhibiting its hydrolysis with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), rescued the IL-1 ~-and LPS-induced reduction of PPARy expression. The 2-AG restoration of the reduced PPARy expression was attenuated by SR141716, a selective CB1 receptor antagonist. Our results suggest that CB1 receptor-dependent PPARy activation and expression are an important and novel signaling pathway in endocannabinoid 2-AG-produced resolution of neuroinflammation in response to proinflammatory insults.
Recommended Citation
Chen, Rongqing; Du, Huizi; Chen, Xiaolei; and Zhang, Jian, "ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL RESOLVING NEUROINFLAMMATION IS MEDIATED BY PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-y" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 7.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/7
ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL RESOLVING NEUROINFLAMMATION IS MEDIATED BY PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-y
Emerging information suggests that endocannabinoids display anti-inflammatory and neuroprotective properties. However, the mechanisms responsible for endocannabinoids in resolving neuroinflammation are largely unknown. We previously demonstrated that 2arachidonoylglycerol (2-AG) protects hippocampal neurons by limiting inflammatory cyclooxygenase-2 (COX-2) expression via a CB1 receptor-dependent MAPK/NF-KB signaling pathway. Here, we show that exogenous and endogenous 2-AG-produced suppressions of NFKB phosphorylation, COX-2 expression and excitatory synaptic transmission in response to proinflammatory interleukin-1 ~ (IL-1 ~) and lipopolysaccharide (LPS) were inhibited by GW9662, a selective peroxisome proliferator-activated receptor-y (PPARy) antagonist, in hippocampal neurons in culture. PPARy agonists 15-deoxy-Ll12'14-prostaglandin J2 (15d-PGJ2) and rosiglitazone mimicked the effects of 2-AG on NF-KB phosphorylation, COX-2 expression and excitatory synaptic transmission, and the effects were eliminated by antagonism of PPARy. Moreover, exogenous application of 2-AG or elevation of endogenous 2-AG by inhibiting its hydrolysis with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), rescued the IL-1 ~-and LPS-induced reduction of PPARy expression. The 2-AG restoration of the reduced PPARy expression was attenuated by SR141716, a selective CB1 receptor antagonist. Our results suggest that CB1 receptor-dependent PPARy activation and expression are an important and novel signaling pathway in endocannabinoid 2-AG-produced resolution of neuroinflammation in response to proinflammatory insults.