| 16000871 |
Kim HJ, Rho YH, Choi SJ, Lee YH, Cheon H, Um JW, Sohn J, Song GG, Ji JD: 15-Deoxy-delta12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes. Exp Mol Med. 2005 Jun 30;37(3):179-85.
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-PGJ (2) 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-PGJ (2) in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ (2) 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 PPARgamma-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 PPARgamma-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-kappaB in lymphocytes. |
4(0,0,0,4) |