Toll-Like Receptors in Ischaemia and Its Potential Role in the Pathophysiology of Muscle Damage in Critical Limb Ischaemia

Figure 1

TLR signalling pathway. MyD88-dependent signalling pathway is used by all TLRs except TLR 3. Signalling through the MyD88-dependent pathway leads to the activation of MAPKK and IKK complex resulting in activation and nuclear translocation of AP-1 and NF-κB, respectively. TLR 4 is capable of signalling through the MyD88-independent pathway as well; however this is the sole signalling mechanism for TLR 3. TRIF is the main adaptor protein in the MyD88-independent pathway and can associate with TRAF6 to activate AP-1 and NF-κB. Alternatively it also activates NF-κB by interacting with RIP-1. TRIF can further interact with TRAF3 and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway resulting in the nuclear translocation of IRF3 and IRF2, respectively.