Figure 8.

TAK-242 inhibits both MyD88-dependent and -independent signalling. DCs from wild-type and MyD88-knockout mice were incubated with various concentrations of TAK-242 for 1 h, then stimulated with LPS. (A) Effect of TAK-242 on the IL-12 p40 and TNF-α production in LPS-induced DCs. DCs were stimulated for 24 h with 10 ng·mL⁻¹ LPS. IL-12 p40 and TNF-α production were measured by ELISA. Data represent the mean in duplicate wells. (B) Effect of TAK-242 on CD40 expression in LPS-induced DCs. DCs were stimulated for 24 h with 10 ng·mL⁻¹ LPS. Cells were stained with PE-conjugated CD40 Ab and analysed with a flow cytometer. Representative data are shown. (C) Effect of TAK-242 on the expression of IFN-inducible genes in LPS-stimulated DCs. DCs were stimulated with 10 ng·mL⁻¹ LPS for the indicated times. Total RNA was subjected to northern blotting with probes for IP-10, GARG16, IRG1 and β-actin. DCs, dendritic cells; GARG16, glucocorticoid-attenuated response gene 16; IL, interleukin; IP-10, IFN-inducible protein 10; IRG1, immune-responsive gene 1; LPS, lipopolysaccharide; TNF-α, tumour necrosis factor-α.