The class I p110 isoforms of PI3K positively regulate CpG- and LPS-induced TNF-α and IL-6 production except for p110β, which negatively regulates IL-6 production. (A) SHIP^+/+ (□) and SHIP^−/− (■) BMmφs were pretreated with 14 μM LY, 50 nM W, or 0.1% DMSO (C) for 30 minutes before stimulation with 30 nM CpG or 10 ng/mL LPS and 3 hours cell supernatants assessed for TNF-α and IL-6 by ELISA. Results are the mean plus or minus SEM of 3 independent experiments assayed in duplicate. *P < .02 compared with vehicle. (B) SHIP^+/+ (□) and SHIP^−/− (■) BMmφs were pretreated with 10 μM PI3K p110 isoform specific inhibitors 1 through 7 or with 0.1% DMSO (sol) or without (C) vehicle control for 30 minutes before stimulation with 30 nM CpG or 10 ng/mL LPS and 24 hours cell supernatants assessed for TNF-α and IL-6 by ELISA. Results are the mean plus or minus SEM of 3 independent experiments assayed in duplicate. *P < .05. (C) 5 × 10⁴/mL SHIP^+/+ BMmφs were exposed to 14 μM LY (●), 50 nM W (■), or 10 μM of p110 isoform specific inhibitor (1 = ▴, 2 = ▾, 3 = ♦, 4 = š, 5 =‖≤, 6 = Δ, 7 =■) for the times indicated and viable cell counts determined using trypan blue and a hemocytometer.