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Biochem Biophys Res Commun. 2000 Jan 7;267(1):329-33.

Parthenolide inhibits activation of signal transducers and activators of transcription (STATs) induced by cytokines of the IL-6 family.

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Institute of Molecular Biology, Jagiellonian University, 3 Mickiewicza Avenue, Krakow, 31-120, Poland.


Progression of inflammatory processes correlates with the release of cell-derived mediators from the local site of inflammation. These mediators, including cytokines of the IL-1 and IL-6 families, act on host cells and exert their action by activating their signal transduction pathways leading to specific target gene activation. Parthenolide, a sesquiterpene lactone found in many medical plants, is an inhibitor of IL-1-type cytokine signaling that blocks the activation of NF-kappaB. Here we show that parthenolide is also an effective inhibitor of IL-6-type cytokines. It inhibits IL-6-type cytokine-induced gene expression by blocking STAT3 phosphorylation on Tyr705. This prevents STAT3 dimerization necessary for its nuclear translocation and consequently STAT3-dependent gene expression. This is a new molecular mechanism of parthenolide action that additionally explains its anti-inflammatory activities.

[Indexed for MEDLINE]

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