Figure 5.

Inhibition of p110δ in BMDCs augments the production of proinflammatory cytokines while inhibiting IFN-β and the products of interferon-stimulated genes. (a) Cytokine concentrations in supernatants of wild-type and δ(D910A) BMDCs stimulated for 24 h with various concentrations of LPS (horizontal axes). *P < 0.05 and **P < 0.005 (Mann-Whitney U-test). (b) IL-12p40 concentrations in culture supernatant of wild-type and δ(D910A) BMDCs pretreated for 1 h with various PI(3)K inhibitors (below), followed by stimulation for 24 h with LPS (100 ng/ml). *P < 0.05 (Mann-Whitney U-test). (c) IL-12p40 concentration in supernatants of wild-type and δ(D910A) splenocytes left unstimulated (Med) or stimulated with LPS (100 ng/ml). *P < 0.05 (Mann-Whitney U-test). (d) IL-12p40 concentration in wild-type and δ(D910A) BMDCs left unstimulated (None) or stimulated with various TLR ligands (horizontal axis) or IL-1β (20 ng/ml) or TNF (20 ng/ml). SM, S. minnesota; EC, E. coli; MPLA, monophosphoryl lipid A; LTA, lipoteichoic acid. *P < 0.05 (Mann-Whitney U-test). (e) Concentration of IFN-β and RANTES in supernatant of wild-type and δ(D910A) BMDCs, as well as wild-type BMDCs treated with IC87114 (0.5 μM; WT + IC87114), left unstimulated (Med) or stimulated with LPS or monophosphoryl lipid A. U, undetectable. *P < 0.05 (analysis of variance). (f) Concentration of IFN-β and IL-10 in supernatants of wild-type and δ(D910A) splenocytes left unstimulated (Med) or stimulated with LPS (100 ng/ml). *P < 0.05 (Mann-Whitney U-test). Data are representative of three experiments (a–d; mean ± s.d. of five mice per group in a; mean and s.d. of five to six mice per group in b; mean and s.d. in c; and mean and s.d. of five mice per group in d) or two experiments (e,f; mean and s.d. of five mice per group (e) or five to six mice per group (f)).