Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 6, Pages 2918-2929Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0900439
Keywords
-
Categories
Funding
- Council of Scientific and Industrial Research, India
- Department of Science and Technology
- Department of Biotechnology, Government of India
Ask authors/readers for more resources
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 I kappa B alpha 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-kappa B. We demonstrate that NAC at 3 mM concentration could increase bacillus Calmette-Guerin-induced IFN-gamma production by PBMCs from patients with active tuberculosis and shifts the anti-bacillus Calmette-Guerin 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. The Journal of Immunology, 2010, 184: 2918-2929.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available