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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 |
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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] |
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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] |
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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] |
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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] |
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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 |
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