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.

Details

Title
Characterization of Endocannabinoid-Metabolizing Enzymes in Human Peripheral Blood Mononuclear Cells under Inflammatory Conditions
Author
Szafran, Brittany N 1 ; Lee, Jung Hwa 1 ; Borazjani, Abdolsamad 1 ; Morrison, Peter 2 ; Zimmerman, Grace 2   VIAFID ORCID Logo  ; Andrzejewski, Kelly L 3 ; Ross, Matthew K 1   VIAFID ORCID Logo  ; Kaplan, Barbara LF 1   VIAFID ORCID Logo 

 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 
 Department of Neurology, University of Rochester, Rochester, NY 14627, USA; Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY 14211, USA 
First page
3167
Publication year
2018
Publication date
2018
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2582832946
Copyright
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.