PMID- 21511917
OWN - NLM
STAT- MEDLINE
DCOM- 20110916
LR  - 20211020
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 80
IP  - 1
DP  - 2011 Jul
TI  - 15-Deoxy-delta12,14-prostaglandin J2-glycerol ester, a putative metabolite of 
      2-arachidonyl glycerol, activates peroxisome proliferator activated receptor 
      gamma.
PG  - 201-9
LID - 10.1124/mol.110.070441 [doi]
AB  - 2-Arachidonyl glycerol (2-AG) is an endogenous arachidonic acid derivative 
      capable of suppressing interleukin (IL)-2 production by activated T cells. 
      2-AG-mediated IL-2 suppression is dependent on cyclooxygenase-2 (COX-2) 
      metabolism and peroxisome proliferator activated receptor gamma (PPARgamma) activation. 
      The objective of the present studies was to examine whether 
      15-deoxy-Delta(12,14)-PGJ(2)-glycerol ester (15d-PGJ(2)-G), a putative metabolite of 
      2-AG, can mimic the actions of 2-AG on IL-2 regulation through PPARgamma activation. 
      15d-PGJ(2)-G bound PPARgamma-ligand binding domain in a PPARgamma competitive binding 
      assay. 15d-PGJ(2)-G treatment activated PPARgamma in a reporter assay, and PPARgamma 
      activation was attenuated when a PPARgamma antagonist, 
      2-chloro-5-nitro-N-4-pyridinylbenzamide (T0070907), was present. 15d-PGJ(2)-G 
      treatment suppressed IL-2 production by activated Jurkat cells, which was 
      partially attenuated when pretreated with T0070907. Moreover, IL-2 suppression 
      was pronounced when 15d-PGJ(2)-G was present 30 min before or after T-cell 
      activation. Concordant with IL-2 suppression, 15d-PGJ(2)-G treatment decreased 
      nuclear factor of activated T cells (NFAT) transcriptional activity in 
      transiently transfected Jurkat cells. It is noteworthy that T0070907 alone 
      markedly increased NFAT reporter activity, suggesting the existence of endogenous 
      PPARgamma activation and modulation of NFAT. Because COX-2 metabolism of 2-AG is 
      important for IL-2 suppression, the effect of 2-AG on COX-2 and PPARgamma mRNA 
      expression was investigated. 2-AG treatment decreased the up-regulation of COX-2 
      mRNA after T-cell activation, which suggests negative feedback limiting 
      COX-2-mediated metabolism of 2-AG. PPARgamma mRNA expression was increased upon 
      activation, and 2-AG treatment produced a modest decrease in PPARgamma mRNA 
      expression. Collectively, our findings suggest that 15d-PGJ(2)-G activates PPARgamma 
      to decrease NFAT transcriptional activity and IL-2 expression in activated T 
      cells.
FAU - Raman, Priyadarshini
AU  - Raman P
AD  - Department of Pharmacology & Toxicology and the Center for Integrative 
      Toxicology, Michigan State University, East Lansing, Michigan 48824-1317, USA.
FAU - Kaplan, Barbara L F
AU  - Kaplan BL
FAU - Thompson, Jerry T
AU  - Thompson JT
FAU - Vanden Heuvel, John P
AU  - Vanden Heuvel JP
FAU - Kaminski, Norbert E
AU  - Kaminski NE
LA  - eng
GR  - R01 DA012740/DA/NIDA NIH HHS/United States
GR  - R01-DA12740/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110421
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (15-deoxy-delta(12,14)-prostaglandin J2)
RN  - 0 (Interleukin-2)
RN  - 0 (PPAR gamma)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Interleukin-2/antagonists & inhibitors
MH  - Jurkat Cells
MH  - PPAR gamma/*drug effects
MH  - Prostaglandin D2/*analogs & derivatives/metabolism/pharmacology
PMC - PMC3127542
EDAT- 2011/04/23 06:00
MHDA- 2011/09/17 06:00
PMCR- 2012/07/01
CRDT- 2011/04/23 06:00
PHST- 2011/04/23 06:00 [entrez]
PHST- 2011/04/23 06:00 [pubmed]
PHST- 2011/09/17 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - mol.110.070441 [pii]
AID - 3699074 [pii]
AID - 10.1124/mol.110.070441 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2011 Jul;80(1):201-9. doi: 10.1124/mol.110.070441. Epub 2011 Apr 
      21.