Toll-Like Receptor Signaling Pathways and the Evidence Linking Toll-Like Receptor Signaling to Cardiac Ischemia/Reperfusion Injury

Toll-like receptors (TLRs) play a key role in innate immune defenses. After activation by foreign pathogens or host-derived molecules, TLRs signal via overlapping or distinct signaling cascades and eventually induce numerous genes involved in a variety of cellular responses. A growing body of evidence suggests that TLR signaling also plays an important role in cardiac ischemia/reperfusion injury. We review our current understanding of the TLR signaling pathways and their roles in the pathophysiology of cardiac ischemia/reperfusion injury, as well as discuss several mechanisms for TLR activation and regulation. ABBREVIATIONS-ATF3-activating transcription factor 3; ARM-the HEAT/Armadillo repeats; AP-1-activator protein 1; BTK-Bruton tyrosine kinase; ER-endoplasmic reticulum; I/R-ischemia/reperfusion; IFN-type-1 interferons; IRF-IFN regulatory factor; IRAK-IL-1 receptor-associated protein kinase; LPS-lipopolysaccharide; MSK-mitogen- and stress-activated protein kinase; MyD88-myeloid differentiation primary response gene 88; MAL-MyD88 adaptor-like, also known as TIRAP; NFκB-nuclear factor-κB; PKCε-protein kinase C ε; PRR-pattern-recognizing receptor; SAM-sterile motif α; SARM-sterile α and armadillo motif-containing protein; SIGIRR-single immunoglobulin IL-1R-related molecule; STING-stimulator of interferon genes; SOCS1-suppressor of cytokine signaling 1; TAK1-transforming growth factor-β-activated kinase 1; TGF-transforming growth factor; TRAF6-TNF receptor-associated factor 6; TRAM-TRIF-related adaptor molecule; TRIF-TIR domain-containing adaptor protein-inducing IFN-β; TLR-toll-like receptor; TOLLIP-Toll-interacting protein