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-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-κB in lymphocytes.
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Kim, H., Rho, Y., Choi, S. et al. 15-Deoxy-Δ12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes. Exp Mol Med 37, 179–185 (2005). https://doi.org/10.1038/emm.2005.24
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DOI: https://doi.org/10.1038/emm.2005.24
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