Sesquiterpene Lactones Specifically Inhibit Activation of NF-kappa B by Preventing the Degradation of Ikappa B-alpha and Ikappa B-beta Hehner, S.P.a , Heinrich, M.b , Bork, P.M.b , Vogt, M.c , Ratter, F.a , Lehmann, V.a , Schulze-Osthoff, K.c , Dröge, W.a , Schmitz, M.L.

Hehner, S.P., Heinrich, M., Bork, P.M., Vogt, M., Ratter, F., Lehmann, V., Schulze-Osthoff, K., Dröge, W. and Schmitz, M.L. (1998) Sesquiterpene Lactones Specifically Inhibit Activation of NF-kappa B by Preventing the Degradation of Ikappa B-alpha and Ikappa B-beta Hehner, S.P.a , Heinrich, M.b , Bork, P.M.b , Vogt, M.c , Ratter, F.a , Lehmann, V.a , Schulze-Osthoff, K.c , Dröge, W.a , Schmitz, M.L. Journal of Biological Chemistry, 273 (3). pp. 1288-1297. 10.1074/jbc.273.3.1288.

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DOI: 10.1074/jbc.273.3.1288

Abstract

Extracts from certain Mexican Indian medicinal plants used in traditional indigenous medicine for the treatment of inflammations contain sequiterpene lactones (SLs), which specifically inhibit the transcription factor NF-κB (Bork, P.M., Schmitz, M. L., Kuhnt, M., Escher, C., and Heinrich, M. (1997) FEBS Lett. 402, 85-90). Here we show that SLs prevented the activation of NF-κB by different stimuli such as phorbol esters, tumor necrosis factor-α, ligation of the T-cell receptor, and hydrogen peroxide in various cell types. Treatment of cells with SLs prevented the induced degradation of IκB-α and IκB-β by all these stimuli, suggesting that they interfere with a rather common step in the activation of NF-κB. SLs did neither interfere with DNA binding activity of activated NF-κB nor with the activity of the protein tyrosine kinases p59(fyn) and p60(src). Micromolar amounts of SLs prevented the induced expression of the NF-κB target gent intracellular adhesion molecule 1. Inhibition of NF-κB by SLs resulted in an enhanced cell killing of murine fibroblast cells by tumor necrosis factor- α. Sis lacking an exomethylene group in conjugation with the lactone function displayed no inhibitory activity on NF-κB. The analysis of the cellular redox state by fluorescence-activated cell sorter showed that the SLs had no direct or indirect anti-oxidant properties.

Item Type:Article
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Centre for Pharmacognosy and Phytotherapy
ID Code:2683
Journal or Publication Title:Journal of Biological Chemistry
Deposited By:Library Staff
Deposited On:19 Jan 2012 15:04
Last Modified:19 Jan 2012 15:04

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