The anti-inflammatory effects of the tellurium redox modulating compound, AS101, are associated with regulation of NFB signaling pathway and nitric oxide induction in macrophages

Miri Brodsky, Gilad Halpert, Michael Albeck, Benjamin Sredni

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Abstract

Background. LPS-activated macrophages produce mediators which are involved in inflammation and tissue injury, and especially those associated with endotoxic shock. The non toxic tellurium compound ammonium tri- chloro(dioxoethylene-O,O'-)tellurate, AS101, has been recently shown to exert profound anti-inflammatory properties in animal models, associated with its Te(IV) redox chemistry. This study explores the anti-inflammatory properties of AS101 with respect to modulation of inflammatory cytokines production and regulation of iNOS transcription and expression in activated macrophages via targeting the NFkB complex. Results. AS101 decreased production of IL-6 and in parallel down-regulated LPS-induced iNOS expression and NO secretion by macrophages. AS101 reduced IkB phosphorylation and degradation, and reduced NFkB nuclear translocalization, albeit these effects were exerted at different kinetics. Chromatin immunoprecipitation assays showed that AS101 treatment attenuated p50-subunit ability to bind DNA at the NFkB consensus site in the iNOS promotor following LPS induction. Conclusions. Besides AS101, the investigation of therapeutic activities of other tellurium(IV) compounds is scarce in the literature, although tellurium is the fourth most abundant trace element in the human body. Since IKK and NFkB may be regulated by thiol modifications, we may thus envisage, inview of our integrated results, that Te(IV) compounds, may have important roles in thiol redox biological activity in the human body and represent a new class of anti-inflammatory compounds.

Original languageEnglish
Article number3
JournalJournal of Inflammation
Volume7
DOIs
StatePublished - 20 Jan 2010

Bibliographical note

Funding Information:
This work was partly supported by the Safdié Institute for AIDS and Immunology Research, The Dr. Tovi Comet-Walerstein Research Program, The Dave and Florence Muskovitz Chair in Cancer Research, The Jaime Lusinchi Research Institute in Applied Sciences and by grant No. 3-2994 from the Chief Scientist Office of the Ministry of Health, Israel. This study was a part of the PhD thesis of Miri Brodsky.

Funding

This work was partly supported by the Safdié Institute for AIDS and Immunology Research, The Dr. Tovi Comet-Walerstein Research Program, The Dave and Florence Muskovitz Chair in Cancer Research, The Jaime Lusinchi Research Institute in Applied Sciences and by grant No. 3-2994 from the Chief Scientist Office of the Ministry of Health, Israel. This study was a part of the PhD thesis of Miri Brodsky.

FundersFunder number
Jaime Lusinchi Research Institute in Applied Sciences3-2994
Safdié Institute for AIDS and Immunology Research
Ministry of Health, State of Israel

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