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

Table 2

Summary of the evidence for the role of TLRs in the pathogenesis of tissue damage in ischaemia and I/R injury.

Organ ischaemia and I/R injury	Expression of TLRs	Upregulation of TLRs in ischaemia	Evidence for role of TLR in pathophysiology	Potential endogenous ligand implicated in pathogenesis
Cerebral	Glial cells: TLR 1–9 [32, 33]; Neurons: TLR 2 and 4 [34]	TLR 2, 4 and 9 [34, 35]	TLR 2 and 4 knockout mice have reduced infarct size following ischaemia [34, 36–38]	HSP 70 [34]
Liver	Hepatocytes: TLR 2, 3, 4 and 5 [39]; Non-parenchymal cells: TLR 2, 3, 4, 5, 7 and 9 [39]	TLR 2 [40]	TLR 4 and 9 knockout mice are protected against ischaemia-induced liver injury [41–43]	HSP 72 [44] and HMGB-1 [42, 45]
Renal	Parenchyma: TLRs 1–10 at varying detection levels [46–48]	TLR 2 and 4 [47, 49]	TLR 2 and 4 knockout mice are protected against renal I/R injury, and this is associated with a reduction in inflammatory cytokine levels [49–52]	HMGB-1, hyaluronan and biglycan [49, 51, 53]
Myocardial	Myocytes: TLR 2, 3, 4 and 6 [54]	TLR 4 [55]	TLR 2- and 4-deficient mice show reduced myocardial infarct size [56–59]. TLR 4 antagonist eritoran leads to reduced infarct size, NF-κB nuclear translocation, and proinflammatory cytokine expression [60]	HMGB-1 [61]
Skeletal muscle	TLR 1–9 [62–64]	TLR 2, 4, 6 [65]	TLR 2 antagonsim reduces pro-inflammatory cytokine expression in an in vitro model of skeletal muscle ischaemia [65]	Under investigation