15-Deoxy-delta12,14-PGJ2inhibits IL-6-induced Stat3 phosphorylation in lymphocytes.
- Author:
Hyo Jin KIM
1
;
Young Hee RHO
;
Seong Jai CHOI
;
Young Ho LEE
;
Hyeon Joo CHEON
;
Jun Won UM
;
Jeongwon SOHN
;
Gwan Gyu SONG
;
Jong Dae JI
Author Information
1. Department of Microbiology and Immunology College of Medicine, Korea University Seoul 136-705, Republic of Korea. jjdjmesy@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
15-deoxy-delta(12,14)-prostaglandin J2;
Interleukin-6;
inflammation mediators;
lymphocytes;
PPARgammar;
Stat1 protein;
Stat3 protein
- MeSH:
Arthritis, Rheumatoid/metabolism/pathology;
Chromans/pharmacology;
Cycloheximide/pharmacology;
DNA-Binding Proteins/*metabolism;
Dactinomycin/pharmacology;
Gene Expression Regulation;
Humans;
Hypoglycemic Agents/pharmacology;
Interleukin-6/*pharmacology;
Jurkat Cells/metabolism/pathology;
Lymphocytes/cytology/*drug effects/*metabolism;
NF-kappa B/metabolism;
PPAR gamma/metabolism;
Phosphorylation;
Prostaglandin D2/*analogs & derivatives/pharmacology;
Protein Synthesis Inhibitors/pharmacology;
Research Support, Non-U.S. Gov't;
*Signal Transduction;
Thiazolidinediones/pharmacology;
Trans-Activators/*metabolism
- From:Experimental & Molecular Medicine
2005;37(3):179-185
- CountryRepublic of Korea
- Language:English
-
Abstract:
15-deoxy-delta12,14-PGJ2(15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear receptor family implicated in regulation of lipid metabolism and adipocyte differentiation. Recent studies have shown that 15d-PGJ2 is the potent anti-inflammatory agent functioning via PPARgamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ2 in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ2 blocked IL-6 induced Stat1 and Stat3 activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min after treatment of 15d-PGJ2. Other PPARgamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ2 affect the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism. Although cycloheximide reversed 15d-PGJ2-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression. These results show that 15d-PGJ2 specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ2 may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappaB in lymphocytes.
