Fig. 2.

Tumor promoter TPA directly activates IDO expression and cooperates with pro-inflammatory regulators IFN-γ, LPS, and IL-1β to superactivate IDO expression. Human U937 cells were untreated or treated with 100 ng/ml TPA in the absence or presence of known immune and/or IDO-activating stimuli. Culture media were harvested 24 h later to quantitate relative levels of kynurenine by LC/MS as analyzed in triplicate. The stimuli included IFN-γ (100 ng/ml), TGF-β (50 ng/ml), IL-1β (5 ng/ml), TNF-α (10 ng/ml), alum (100 μg/ml), genomic E. coli DNA (9.5 μg/ml), imiquimod (3 μg/ml), lipopolysaccharide (LPS; 100 ng/ml), poly dI:dC (10 μg/ml), heat-killed S. aureus (1.5 × 10⁸ bacteria/ml), or HMGB1 (3 μg/ml). Additive effects are apparent between TPA (dot) and the stronger IDO inducers IFN-γ and LPS (carots) or the weaker inducer IL-1β (asterisk). The experiment was repeated once with similar results