title: Lipopolysaccharide suppresses carboxylesterase 2g activity and 2-arachidonoylglycerol hydrolysis: A possible mechanism to regulate inflammation.
abstract: Inflammation is an important part of the innate immune response and is involved in the healing of many disease processes; however, chronic inflammation is a harmful component of many diseases. The regulatory mechanisms of inflammation are incompletely understood. One possible regulatory mechanism is the endocannabinoid system. Endocannabinoids such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA) are generally anti-inflammatory via engagement of the cannabinoid receptor 2 (CB2) on innate cells; therefore, preventing the degradation of endocannabinoids by specific serine hydrolases such as fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and carboxylesterases (CES) might decrease inflammation. We hypothesized that the activities of these catabolic enzymes would decrease with a subsequent increase in 2-AG and AEA in a model of inflammation. Mice were injected with lipopolysaccharide (LPS) for 6 or 24h, and inflammation was confirmed by an increase in interleukin-6 (il6) and il17 gene expression. Activity-based protein profiling (ABPP) of serine hydrolases showed no significant difference in various serine hydrolase activities in brain or liver, whereas a modest decrease in Ces activity in spleen after LPS administration was noted. 2-AG hydrolase activity in the spleen was also decreased at 6h post LPS, which was corroborated by LPS treatment of splenocytes ex vivo. ABPP-MudPIT proteomic analysis suggested that the decreased 2-AG hydrolysis in spleen was due to a reduction in Ces2g activity. These studies suggest that the endocannabinoid system could be activated via suppression of a 2-AG catabolic enzyme in response to inflammatory stimuli as one mechanism to limit inflammation.
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
authors.forename: Brittany
authors.initials: B
authors.lastname: Szafran
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
authors.forename: Abdolsamad
authors.initials: A
authors.lastname: Borazjani
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Ross
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, United States. Electronic address: barbara.kaplan@msstate.edu.
authors.forename: Barbara L F
authors.initials: BL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000819:agonists / Q000378:metabolism*; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D063388:Endocannabinoids / Q000819:agonists / Q000378:metabolism*; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004794:Enzyme Repression / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005989:Glycerides / Q000819:agonists / Q000378:metabolism*; D006868:Hydrolysis / Q000187:drug effects; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011897:Random Allocation; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013379:Substrate Specificity; D000093242:Interleukin-6 Inhibitors
chemical_list: D001095:Arachidonic Acids; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases; D063388:Endocannabinoids; D005989:Glycerides; D020381:Interleukin-17; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008994:Monoacylglycerol Lipases; D000093242:Interleukin-6 Inhibitors; C098680:Il17a protein, mouse; C577686:interleukin-6, mouse; C094503:glyceryl 2-arachidonate; C500145:Ces2c protein, mouse; C000611560:Ces2g protein, mouse
keywords: 2-Arachidonylglycerol; Activity-based protein profiling; Carboxylesterase; Endocannabinoid; Inflammation