Protective effect of toll-interacting protein overexpression against paraquat-induced lung injury in mice and A549 cells through inhibiting oxidative stress, inflammation, and NF-κB signaling pathway

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-113 (IL-113) 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 PQtreated A549 cells. Meanwhile, Tollip overexpression lowered the level of IL-113 and decreased the protein expressions of p-p65 in the cytoplasm and nuclear p65. Importantly, inhibition of NF-kappa B signaling pathway probably by decreasing NF-kappa B 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-kappa B signaling pathway activation, which provided some novel ideas for the treatment of lung damage mediated by PQ.

Automated summary

Tollip overexpression can reduce inflammatory cell infiltration, decrease inflammation, and suppress the activation of the NF-κB signaling pathway.