IFN-gamma and pro-inflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension.
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.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D000860:Hypoxia / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010084:Oxidation-Reduction
D016207:Cytokines; D020382:Interleukin-18; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D005978:Glutathione