In:
European Journal of Immunology, Wiley, Vol. 46, No. 6 ( 2016-06), p. 1472-1479
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.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201546181
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
1491907-2
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