PMID- 27064137
OWN - NLM
STAT- MEDLINE
DCOM- 20170629
LR  - 20181202
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 46
IP  - 6
DP  - 2016 Jun
TI  - Production of endocannabinoids by activated T cells and B cells modulates 
      inflammation associated with delayed-type hypersensitivity.
PG  - 1472-9
LID - 10.1002/eji.201546181 [doi]
AB  - 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 naive 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 naive 
      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-alpha, 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.
CI  - (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Sido, Jessica M
AU  - Sido JM
AD  - Department of Pathology, Microbiology, & Immunology, University of South Carolina 
      School of Medicine, Columbia, SC, USA.
FAU - Nagarkatti, Prakash S
AU  - Nagarkatti PS
AD  - Department of Pathology, Microbiology, & Immunology, University of South Carolina 
      School of Medicine, Columbia, SC, USA.
FAU - Nagarkatti, Mitzi
AU  - Nagarkatti M
AD  - Department of Pathology, Microbiology, & Immunology, University of South Carolina 
      School of Medicine, Columbia, SC, USA.
AD  - WJB Dorn Veterans Affairs Medical Center, Columbia, SC, USA.
LA  - eng
GR  - I01 BX001357/BX/BLRD VA/United States
GR  - R01 MH094755/MH/NIMH NIH HHS/United States
GR  - R01 ES019313/ES/NIEHS NIH HHS/United States
GR  - P20 GM103641/GM/NIGMS NIH HHS/United States
GR  - P01 AT003961/AT/NCCIH NIH HHS/United States
GR  - R01 AT006888/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Arachidonic Acids)
RN  - 0 (Cytokines)
RN  - 0 (Endocannabinoids)
RN  - 0 (Glycerides)
RN  - 0 (Receptors, Cannabinoid)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
SB  - IM
MH  - Animals
MH  - Arachidonic Acids/metabolism/pharmacology
MH  - B-Lymphocytes/*immunology/*metabolism
MH  - Cytokines/metabolism
MH  - Endocannabinoids/*biosynthesis/metabolism/pharmacology
MH  - Female
MH  - Glycerides/metabolism/pharmacology
MH  - Hypersensitivity, Delayed/drug therapy/*immunology/*metabolism
MH  - Immunomodulation/drug effects
MH  - Lymphocyte Activation/*immunology
MH  - Mice
MH  - Receptors, Cannabinoid/metabolism
MH  - T-Lymphocytes/*immunology/*metabolism
PMC - PMC5206973
MID - NIHMS833509
OTO - NOTNLM
OT  - Anti-inflammatory
OT  - Cannabinoid receptor
OT  - Delayed-type hypersensitivity (DTH)
OT  - Endocannabinoids
OT  - Th1
OT  - Th17
OT  - T cell suppression
COIS- The authors declare no commercial or finical conflict of interest.
EDAT- 2016/04/12 06:00
MHDA- 2017/07/01 06:00
PMCR- 2017/06/01
CRDT- 2016/04/12 06:00
PHST- 2015/11/06 00:00 [received]
PHST- 2016/02/29 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/12 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - 10.1002/eji.201546181 [doi]
PST - ppublish
SO  - Eur J Immunol. 2016 Jun;46(6):1472-9. doi: 10.1002/eji.201546181.