Fig. 3

A negative feedback cross talk between PI3Kα/Akt and NF-κB signaling pathway by a local brief stimulation of TLR9, a potent preconditioning tool for programming the subsequent responses to I/R injuries and stimulation by TLR2, TLR4, or TLR5 ligands. TLR9 ligation with CpG-DNA leads to receptor tyrosine phosphorylation and subsequent activation of the p85 subunit of PI3K. The PI3K-α/Akt pathway is subsequently activated in response to TLR9 ligation. Activation of PI3K/Akt pathway protects cells against apoptosis, through up-regulation of the NF-κB pathway inhibitors TNFAIP3/TNIP1/NFKBIA/TRIM30. TLR9 agonist activates both NF-κB and PI3K/Akt signaling pathway. TLR moderate activation directs to PI3K/Akt pathway through up-regulating NF-κB pathway inhibitors TNFAIP3, its associated protein TNIP1, NFKBIA, and also an additional inhibitor TRIM30a, to inhibit inflammatory pathway. Activation of PI3K/Akt signaling protects cells against apoptosis, through further up-regulation of the NF-κB pathway inhibitors TNFAIP3/TNIP1/NFKBIA/TRIM3. TLR9 signaling acts as a dominant activator of the isoform PI3Kα-Akt pathway during I/R injury and in the preconditioning mechanism