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. 2010 Dec 14;286(7):5823–5835. doi: 10.1074/jbc.M110.192393

FIGURE 8.

FIGURE 8.

Signaling integration through cross-talk of the Notch1-PI3K and PKC-MAPK axis is critical for NOD2-mediated resolution of inflammation. A, quantitative real time PCR analysis for Bcl-xL, cIAP1, and XIAP expression upon stimulation of NOD2 with MDP, with or without pretreatment with PP2, GSI-I, or LY294002 or chelerythrine, U0126, or p38 MAP kinase inhibitor or Bay 11-7082. B and C, MTT assay performed on TNF-α (B) (200 ng/ml) or IFN-γ (C) (1000 ng/ml) treated macrophages shows a significant decrease in apoptotic cells upon NOD2 stimulation with MDP. Pharmacological inhibition of NOD2 (PP2), Notch1 (GSI-I), PI3K (LY294002), PKC (chelerythrine), or NF-κB (Bay 11-7082) abrogated the suppressive effect of MDP. The data are represented as mean ± S.E. from three independent experiments. Med, medium; *, p < 0.05 versus MDP; **, p < 0.05 versus TNF-α or IFN-γ; ***, p < 0.05 versus TNF-α + MDP or IFN-γ + MDP.