15-deoxy-Delta(12,14)-PGJ(2) inhibits IL-6-induced Stat3 phosphorylation in lymphocytes
- Authors
- Kim, HJ; Rho, YH; Choi, SJ; Lee, YH; Cheo, HJ; Um, JW; Sohn, J; Song, GG; Ji, JD
- Issue Date
- 30-Jun-2005
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- 5-deoxy-delta(12,14)-prostaglandin J(2); interleukin-6; inflammation mediators; lymphocytes; PPAR gamma; Stat1 protein; Stat3 protein
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.37, no.3, pp 179 - 185
- Pages
- 7
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 37
- Number
- 3
- Start Page
- 179
- End Page
- 185
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/19638
- DOI
- 10.1038/emm.2005.24
- ISSN
- 1226-3613
2092-6413
- Abstract
- 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) 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 PPAR gamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPAR gamma agonists are involved in inhibiting NF-kappa B signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ(2) in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPAR gamma. 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-PGJ(2). Other PPAR gamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ(2) affect the IL-6-induced Jak-Stat signaling pathway via PPAR gamma-independent mechanism. Although cycloheximide reversed 15d-PGJ(2)-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ(2)-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-PGJ(2) specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ(2) may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappa B in lymphocytes.
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- Appears in
Collections - 1. Basic Science > Department of Biochemistry and Molecular Biology > 1. Journal Articles
- 2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles
- 2. Clinical Science > Department of Rheumatology > 1. Journal Articles
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