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

Research output: Contribution to journalArticle

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

Fingerprint

Phosphorylation
Lymphocytes
Interleukin-6
Peroxisome Proliferator-Activated Receptors
troglitazone
Anti-Inflammatory Agents
Chemical activation
9-deoxy-delta-9-prostaglandin D2
Jurkat Cells
Dactinomycin
Cycloheximide
Cytoplasmic and Nuclear Receptors
Nuclear Family
Lipid Metabolism
Adipocytes
Gene expression
Rheumatoid Arthritis
B-Lymphocytes
Inhibition (Psychology)
Ligands

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

Cite this

15-Deoxy-Δ12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes. / Kim, Hyo Jin; Rho, Young Hee; Choi, Sungjae; Lee, Young Ho; Cheon, Hyeon Joo; Um, Jun Won; Sohn, Jeongwon; Song, Gwan Gyu; Ji, Jong Dae.

In: Experimental and Molecular Medicine, Vol. 37, No. 3, 30.06.2005, p. 179-185.

Research output: Contribution to journalArticle

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AU - Rho, Young Hee

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AU - Cheon, Hyeon Joo

AU - Um, Jun Won

AU - Sohn, Jeongwon

AU - Song, Gwan Gyu

AU - Ji, Jong Dae

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