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Eur J Immunol. 2002 Oct;32(10):2866-73.

IFN-gamma and pro-inflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension.

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Basic Research Laboratories, Ajinomoto Co. Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210, Japan.


Murine mature splenic DC with elevated intracellular glutathione, pretreated with IL-18, strikingly augmented the production of IFN-gamma in response to IL-12, whereas intracellular glutathione deprivation ablated this effect of IL-18. Likewise, macrophages with elevated intracellular glutathione augmented IFN-gamma production upon LPS or IL-12+IL-18 stimulation, whereas macrophages with reduced intracellular glutathione showed the reciprocal response. Under hypoxia, macrophages displayed a functional phenotype with decreased intracellular glutathione, i.e. decreased NO and IL-12, and elevated IL-10 production. However, mature DC and macrophages produced an elevated amount of IFN-gamma under hypoxia. Taken together, our results suggest that the intracellular redox status of DC and macrophages may play a pivotal role in local innate immunity, depending on local oxygen tension.

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