15-Deoxy-Δ12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes

Hyo Jin Kim, Young Hee Rho, Sungjae Choi, Young Ho Lee, Hyeon Joo Cheon, Jun Won Um, Jeongwon Sohn, Gwan Gyu Song, Jong Dae Ji

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15 Citations (Scopus)

Abstract

15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) γ, 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 PPARγ-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARγ agonists are involved in inhibiting NF-κB 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 PPARγ. 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 PPARγ-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 PPARγ-independent mechanism. Although cycloheximide reversed 15d-PGJ 2-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-κB in lymphocytes.

Original languageEnglish
Pages (from-to)179-185
Number of pages7
JournalExperimental and Molecular Medicine
Volume37
Issue number3
Publication statusPublished - 2005 Jun 30

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Keywords

  • 15-deoxy-delta(12,14)-prostaglandin J
  • Inflammation mediators
  • Interleukin-6
  • Lymphocytes
  • PPARγ
  • Stat1 protein
  • Stat3 protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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