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Glutathione Downregulates the Phosphorylation of IκB: Autoloop Regulation of the NF-κB-Mediated Expression of NF-κB Subunits by TNF-α in Mouse Vascular Endothelial Cells☆

https://doi.org/10.1006/bbrc.1998.9697Get rights and content

Abstract

Nuclear factor-kappa B (NF-κB) regulates gene expression upon immune and inflammatory responses. It has been demonstrated that redox regulation by thiols is involved in the signal-transduction cascade. In this study, we examined the effect of glutathione (GSH) on the NF-κB activity and the expression of NF-κB subunits induced by tumor necrosis factor-α (TNF-α) using mouse vascular endothelial cells. GSH inhibited the serine phosphorylation of IκB-α by TNF-α, leading to the downregulation of NF-κB-DNA binding activity followed by decreased expression of p65/p50 and IκB mRNAs. The regulation of the autoregulatory loop for the NF-κB activation and the expression of NF-κB subunits may be important in endothelial cells in response to cytokines.

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Abbreviations used: GSH, glutathione (γ-glutamylcysteinyl glycine); NF-κB, nuclear factor-κB; IκB, inhibitory molecule of NF-κB; MHE, mouse hemangioendothelioma; GAPDH, glyceraldehyde 3-phosphate dehydrogenase

1

To whom correspondence should be addressed at Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan. Fax: ++81-95-849-7100. E-mail:[email protected].

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