TLR3 is involved in paraquat-induced acute renal injury

Abstract

AimsTo investigate the role of Toll-like receptor 3 (TLR3) in mouse paraquat-induced acute renal injury. Materials and methodsAcute renal injury was established in C57BL/6J mice by intraperitoneal injection of paraquat (28 mg/kg). The mice were also injected intraperitoneally with TLR3 agonist poly I:C (20 mg/kg) or TLR3/dsRNA complex inhibitor (1 mg) 1 h before paraquat exposure. At 72 hour post paraquat exposure, the mice were sacrificed and the blood and renal tissues were collected to examine TLR3 expression in renal tissues, pathological injury in renal tissues, renal function, inflammation, and cell apoptosis. Key findingsAfter paraquat exposure, TLR3 expression in mouse renal tissues was significantly increased, and pathological changes to the renal tissues and remarkable renal impairment were present. Compared to the paraquat group, the poly I:C group showed no significant difference in renal pathology, renal function, inflammation, or cell apoptosis. However, TLR3 inhibitor treatment significantly alleviated injury to the renal tissues, improved renal function, inhibited NF-κB activation, suppressed the infiltration of neutrophils, and lessened the expression of IL-1β, TNF-α, and keratinocyte chemoattractant (KC) in renal tissues. TLR3 inhibitor treatment also suppressed the activation of caspase-8 and caspase-3 and reduced apoptosis in the renal tissues. SignificanceParaquat exposure significantly upregulates TLR3 expression in renal tissues, and activation of the TLR3 signaling pathway is an important contributor to paraquat nephrotoxicity. TLR3 activation exacerbates inflammation and cell apoptosis in renal tissues by activating NF-κB and caspase-8, thus promoting paraquat-induced acute renal injury.