Toll-Like Receptor 4 in Experimental Kidney Transplantation: Early Mediator of Endogenous Danger Signals

Abstract

The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression – restricted to the glomerular compartment – was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis.

Curcumin prevents diabetic nephropathy against inflammatory response via reversing caveolin-1 Tyr14 phosphorylation influenced TLR4 activation

“…Activation of renal TLR4 mediates many signaling pathways, which leads to transcriptional expression of chemokines and pro-inflammatory cytokines. And all these inflammatory biomarkers might aggravate kidney injury in acute and chronic kidney diseases [26][27][28][29][30][31][32][33]. We found a significant negative correlation between TLR4 expression and renal function, which may implicate the contribution of HG to the increased TLR4 expression and proinflammatory cytokines.…”

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

“…Due to the reaction to oxidative stress in kidney IRI, the TLR4 signaling pathway is activated and expressed at a high level, causing a severe infiltration of inflammatory cells [20]. Nuclear factor (NF)-κB is an important transcription factor regulating physiological processes, inflammatory responses, and apoptosis [21].…”

Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury

“…Emerging studies described that TLR4-mediated inflammatory response facilitate renal injuries, especially acute kidney injury [16, 17]. For example, an increased TLR-4 expression was noted in kidneys with ischemia-reperfusion, accompanied with significantly increase of chemokines [18]. Furthermore, in TLR4-deficient mice, less interstitial neutrophil and tubular damage were observed [19].…”