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Molecules 2018, 23(12), 3167; https://doi.org/10.3390/molecules23123167

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

1
Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39759, USA
2
Department of Neurology, University of Rochester, Rochester, NY 14627, USA
3
Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY 14211, USA
*
Authors to whom correspondence should be addressed.
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)
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Abstract

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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