title: Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed-type hypersensitivity.
abstract: Endocannabinoids are endogenous ligands for the cannabinoid (CB) receptors which include anandamide (AEA) and 2-arachidonyl glycerol (2-AG). 2-AG has been linked to inflammation due to its elevated expression in animal models of autoimmunity and hypersensitivity. However, administration of exogenous 2-AG has been shown to suppress inflammation making its precise role unclear. In the current study, we investigated the role of 2-AG following immunization of C57BL/6 (BL6) mice with methylated BSA (mBSA) antigen, which triggers both delayed-type hypersensitivity (DTH) and antibody response. We found that while naïve T cells and B cells expressed low levels of 2-AG, expression significantly increased upon activation. Furthermore, mBSA-immunized mice exhibited higher 2-AG concentration than naïve mice. Exogenous 2-AG treatment (40 mg/kg) in mBSA-immunized mice led to reduced DTH response, and decreased Th1 and Th17-associated cytokines including IL-6, IL-2, TNF-α, and the IgG response. Addition of 2-AG to activated popliteal lymph node (PopLN) cell cultures also inhibited lymphocyte proliferation. Together, these data show for the first time that activated T and B cells produce 2-AG, which plays a negative regulatory role to decrease DTH via inhibition of T-cell activation and proliferation. Moreover, these findings suggest that exogenous 2-AG treatment can be used therapeutically in Th1- or Th17-driven disease.
authors.affiliation: Department of Pathology, Microbiology, & Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Sido
authors.affiliation: Department of Pathology, Microbiology, & Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
authors.affiliation: Department of Pathology, Microbiology, & Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.|WJB Dorn Veterans Affairs Medical Center, Columbia, SC, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D063388:Endocannabinoids / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005989:Glycerides / Q000378:metabolism / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D056747:Immunomodulation / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D043882:Receptors, Cannabinoid / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; C094503:glyceryl 2-arachidonate
keywords: Anti-inflammatory; Cannabinoid receptor; Delayed-type hypersensitivity (DTH); Endocannabinoids; Th1; Th17; T cell suppression