Post-transcriptional study demonstrated that AvrA inhibits the NF-κB activity though stabilizing the inhibitor of NF-κB, IκBα [6, 8]. Overall, this result implies that AvrA suppressed the NF-κB activity

at the early stage of SL1344 infection and has a different regulatory role at the late stage. In contrast, the significance values of SAPK/JNK signaling were low at late stages of SB1117 infection, which suggest that SL1117 infection is not associated with the SAPK/JNK pathway at the late stage of Infection. AvrA regulation of the mTOR, NF-κB, JNK, and oxidative phosphorylation signaling pathways in vivo It is possible that the genes that underlie the biology of a pathway could be different from one observation to another, even if the significant values remain unchanged. To evaluate this possibility, we performed a cross-analysis comparison of the genes associated with a given pathway during the early PI3K Inhibitor Library cost Mocetinostat in vivo and late stages of SL1344 and SB1117 infection. To further analyze the AvrA regulation of the mTOR, NF-κB, JNK, and oxidative phosphorylation signaling pathways in vivo, we generated heat maps to investigate the associated genes in these pathways (Figure 8A-D). Figure 8 Heat maps of Salmonella -responses to gene expression changes involved in four signaling transduction pathways. A: mTOR signaling; B: NF-κB pathway C:SAPK/JNK signaling;

D: Oxidative phosphorylation. Red denotes up-regulation; Green denotes down-regulated genes, black denotes unchanged or P-value > 0.05 in three replicate experiments. As shown in Figure 8A, many genes of mTOR pathway play a role in cell proliferation, migration, apoptosis, differentiation, growth, and cell death. VEGFA, PIK3C2A, PIK3CD, PIK3C2G, and PRKCH showed up-regulation in the SL1344 infection group at the late stage of infection, whereas in the SB1117 infection group, the expression of these genes showed no

significant change. These data indicated that AvrA is involved in the mTOR signaling pathway, thus playing a role in proliferation and apoptosis. Figure 8B showed that Card10 was up-regulated Adenosine at the early stage of SB1117 infection, but not at the early stage of SL1344 infection. The Card10 protein is a caspase recruitment domain/membrane-associated guanylate kinase family that interacts with BCL10 and activates NF-κB-inducing kinase activity [46]. Hence, the result showed that AvrA may inhibit NF-κB activation at the early stage of SL1344 infection relative to SB1117 infection. However, at the late stage of infection, many genes were differentially expressed between the SL1344 vs. SB1117 infection groups. These genes NVP-HSP990 manufacturer including down-regulated KRAS, PIK3R1, PDGFRB, CHR, CHUK and CSNKIA1, as well as up-regulated genes TLR4, TLR3 and TLR7, EIF2AK2, TBk1, and PIK3C2A.