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Alam, K. and Ghousunnissa, S. and Nair, S. and Valluri, V.L. and Mukhopadhyay, Sangita (2010) Glutathione-Redox Balance Regulates c-rel-Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy. The Journal of Immunology, 184 (6). pp. 2918-2929. ISSN 0022-1767

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Abstract

The glutathione-redox balance, expressed as the ratio of intracellular reduced glutathione (GSH) and oxidized glutathione, plays an important role in regulating cellular immune responses. In the current study, we demonstrate that alteration of glutathione-redox balance in macrophages by GSH donors like cell-permeable glutathione ethyl ester reduced or N-acetyl-L-cysteine (NAC) can differentially regulate production of IL-12 cytokine in macrophages. A low concentration of NAC increased IL-12 p40/p70 production, whereas at high concentration, IL-12 production was inhibited due to increased calmodulin expression that binds and sequesters c-rel in the cytoplasm. Although NAC treatment increased the IkappaBalpha phosphorylation, it failed to increase TNF-alpha levels due to enhanced expression of suppressor of cytokine signaling 1, which specifically prevented nuclear translocation of p65 NF-kappaB. We demonstrate that NAC at 3 mM concentration could increase bacillus Calmette-Guérin-induced IFN-gamma production by PBMCs from patients with active tuberculosis and shifts the anti-bacillus Calmette-Guérin immune response toward the protective Th1 type. Our results indicate that redox balance of glutathione plays a critical role in regulating IL-12 induction in native macrophages, and NAC can be used in tailoring macrophages to induce enhanced Th1 response that may be helpful to control tuberculosis and other pathophysiological disorders.

Item Type: Article
Additional Information: [Open Access from the Publisher]
Depositing User: Dr P Divakar
Date Deposited: 28 Aug 2015 05:22
Last Modified: 28 Aug 2015 05:22
URI: http://cdfd.sciencecentral.in/id/eprint/408

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