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Open AccessArticle

Characterization of Endocannabinoid-Metabolizing Enzymes in Human Peripheral Blood Mononuclear Cells under Inflammatory Conditions

Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39759, USA
Department of Neurology, University of Rochester, Rochester, NY 14627, USA
Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY 14211, USA
Authors to whom correspondence should be addressed.
Molecules 2018, 23(12), 3167;
Received: 25 October 2018 / Revised: 20 November 2018 / Accepted: 28 November 2018 / Published: 1 December 2018
(This article belongs to the Special Issue Emerging Topics in (Endo)Cannabinoid Signalling)
Endocannabinoid-metabolizing enzymes are downregulated in response to lipopolysaccharide (LPS)-induced inflammation in mice, which may serve as a negative feedback mechanism to increase endocannabinoid levels and reduce inflammation. Increased plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and decreased fatty acid amide hydrolase (FAAH) activity in peripheral lymphocytes from individuals diagnosed with Huntington’s disease (HD) suggests that a similar negative feedback system between inflammation and the endocannabinoid system operates in humans. We investigated whether CpG- (unmethylated bacterial DNA) and LPS-induced IL-6 levels in peripheral blood mononuclear cells (PBMCs) from non-HD and HD individuals modulated the activities of endocannabinoid hydrolases monoacylglycerol lipase (MAGL) and carboxylesterase (CES). Baseline plasma IL-6 levels and 2-arachidonoylglycerol (2-AG) hydrolytic activity in PBMC lysates were not different in HD and non-HD individuals. Inhibition of MAGL and CES1 activity in PBMCs using the inhibitors JZL184 and WWL113, respectively, demonstrated that MAGL was the dominant 2-AG hydrolytic enzyme in PBMCs, regardless of disease state. Correlative analyses of 2-AG hydrolytic activity versus enzyme abundance confirmed this conclusion. Flow cytometric analysis of PBMCs showed that MAGL and CES1 were primarily expressed in monocytes and to a lesser extent in lymphocytes. In conclusion, these data suggest that IL-6 did not influence 2-AG hydrolytic activity in human PBMCs; however, monocytic MAGL was shown to be the predominant 2-AG hydrolytic enzyme. View Full-Text
Keywords: endocannabinoids; MAGL; CES; Huntington’s disease endocannabinoids; MAGL; CES; Huntington’s disease
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Szafran, B.N.; Lee, J.H.; Borazjani, A.; Morrison, P.; Zimmerman, G.; Andrzejewski, K.L.; Ross, M.K.; Kaplan, B.L. Characterization of Endocannabinoid-Metabolizing Enzymes in Human Peripheral Blood Mononuclear Cells under Inflammatory Conditions. Molecules 2018, 23, 3167.

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