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

Abstract

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.