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. 2007 Jul 11;81(18):9838–9850. doi: 10.1128/JVI.00792-07

FIG. 9.

FIG. 9.

Endogenous NO inactivates IDO in cytokine-treated astrocytes. (A to C) To determine the relationship between iNOS expression and IDO expression in human astrocytes, cells were treated with cytokines (IL-1β, IFN-γ, or together) for 1 to 7 days as indicated and immunoblotted for iNOS and IDO. The results are compared with those obtained with PIC-treated astrocytes. l-NAME (NOS inhibitor) at 100 μM was added to cultures to determine the effect of NO. (D) IDO activity was also determined by measurement of KYN concentrations in day 3 culture supernatants as described in Materials and Methods. Data are means plus SEM from three cases. (E) iNOS activity was determined by measurement of nitrite in day 3 culture supernatants. Data are means plus SEM from four cases. Statistics in panels D and E are repeated-measure ANOVA with Tukey's post hoc test (**, P < 0.01; ***, P < 0.001). KYN induction by both IFN-γ and PIC was significant (P < 0.01 and P < 0.001 versus control). The results show that coinduction of iNOS by the cytokine IL-1 inactivates IDO enzyme in astrocytes without decreasing the amounts of IDO expression.