Toll-interacting protein (Tollip) is a pivotal negative regulator of inflammatory response. In the present study, the effects of Tollip overexpression on paraquat (PQ)-induced lung injury were explored through in vivo and in vitro investigations. Upon stimulation with PQ in mice, the expression of Tollip was down-regulated. Histopathological analysis revealed that the overexpression of Tollip significantly decreased inflammatory cell infiltration. Similarly, the levels of myeloperoxidase (MPO) and interleukin-1β (IL-1β) were lowered by Tollip overexpression in PQ-administrated mice. Besides, the overexpression of Tollip reduced reactive oxygen species (ROS) generation and malondialdehyde (MDA) level but enhanced superoxide dismutase (SOD) activity in PQ-treated A549 cells. Meanwhile, Tollip overexpression lowered the level of IL-1β and decreased the protein expressions of p-p65 in the cytoplasm and nuclear p65. Importantly, inhibition of NF-κB signaling pathway probably by decreasing NF-κB p65-DNA binding activity was induced by Tollip overexpression. Taken together, Tollip overexpression attenuated PQ-initiated lung injury possibly via reduction of oxidative stress and inflammation and suppression of NF-κB signaling pathway activation, which provided some novel ideas for the treatment of lung damage mediated by PQ.

Toll 相互作用蛋白 (Tollip) 是炎症反应的关键负调节因子。在本研究中，通过体内和体外实验探讨了 Tollip 过表达对百草枯 (PQ) 诱导的肺损伤的影响调查。在小鼠中用 PQ 刺激后，Tollip 的表达被下调。组织病理学分析表明，Tollip 的过表达显着减少了炎症细胞浸润。类似地，在 PQ 给药的小鼠中，Tollip 过表达降低了髓过氧化物酶 (MPO) 和白细胞介素-1β (IL-1β) 的水平。此外，在 PQ 处理的 A549 细胞中，Tollip 的过表达减少了活性氧 (ROS) 的产生和丙二醛 (MDA) 的水平，但增强了超氧化物歧化酶 (SOD) 的活性。同时，Tollip 过表达降低了 IL-1β 的水平，并降低了细胞质和核 p65 中 p-p65 的蛋白表达。重要的是，Tollip 过表达可能通过降低 NF-κB p65-DNA 结合活性来抑制 NF-κB 信号通路。综合起来，