Cross talk of the first-line defense TLRs with PI3K/Akt pathway, in preconditioning therapeutic approach

Toll-like receptor family (TLRs), pattern recognition receptors, is expressed not only on immune cells but also on non-immune cells, including cardiomyocytes, fibroblasts, and vascular endothelial cells. One main function of TLRs in the non-immune system is to regulate apoptosis. TLRs are the central mediators in hepatic, pulmonary, brain, and renal ischemic/reperfusion (I/R) injury. Up-regulation of TLRs and their ligation by either exogenous or endogenous danger signals plays critical roles in ischemia/reperfusion–induced tissue damage. Conventional TLR-NF-κB pathways are markedly activated in failing and ischemic myocardium. Recent studies have identified a cross talk between TLR activation and the PI3K/Akt pathway. The activation of TLRs is proposed to be the most potent preconditioning method after ischemia, to improve the cell survival via the mechanism involved the PI3K/Akt signaling pathway and to attenuate the subsequent TLR-NF-κB pathway stimulation. Thus, TLRs could be a great target in the new treatment approaches for myocardial I/R injury.