The STING-IRF3 pathway contributes to paraquat-induced acute lung injury.

Abstract

Immune and inflammatory responses play significant roles in paraquat (PQ)-induced acute lung injury (ALI), but the specific mechanisms remain unclear. Our study aimed to investigate the action of STING-IRF3 signaling on PQ-induced ALI in mice. Following PQ administration, samples were collected at 2, 12, 24, and 48 h for in vivo studies, and 24 h for in vitro studies. Following PQ administration (30 mg/kg, i.p.), injury to mouse lungs was evaluated by H&E staining and wet/dry ratios, and lung oxidative damage was evaluated by MDA and SOD assays. The mRNA levels of Sting, Irf3, and Ifnβ were detected by RT-PCR, the expression of STING and IRF3 were assessed by western blotting and IHC/IF, and the secretion of IFNβ was detected by ELISA. In vivo, PQ administration induced pathological changes and increased wet/dry ratios in lungs after 48 h. Sting, Irf3, and Ifnβ mRNA levels in lung tissues, STING and pIRF3 protein levels in lung tissues, and IFNβ secretion in serum, were upregulated by PQ in a time-dependent manner. PQ administration promoted IRF3 nuclear translocation in lung tissues after 48 h. The above changes were all attenuated by dexamethasone treatment (5 mg/kg, i.p., qd). In vitro, PQ induced STING and IRF3 translocation. Irf3 or Sting silencing decreased the mRNA levels and supernatant secretion of IFNβ in PQ-treated RAW264.7 mouse macrophages. Sting silencing also inhibited the protein and mRNA levels of IRF3 in vitro. Our study suggests that STING-IRF3 signaling contributes to PQ-induced ALI, providing new information for future treatment strategies.

• Authors: Na Wang, Xiaofeng Wang, Yuhua Li, Haitao Shen, Zhenning Liu, Zhongliang Ma, Qiuhe Li, Min Zhao
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 32 Issue 2 Pg. 145-157 (Feb 2022) ISSN: 1537-6524 [Electronic] England
• PMID: 34455893 (Publication Type: Journal Article)

Chemical References

• Interferon Regulatory Factor-3
• Irf3 protein, mouse
• Paraquat

Topics

• Acute Lung Injury (chemically induced)
• Animals
• Interferon Regulatory Factor-3 (genetics)
• Lung
• Mice
• Oxidative Stress
• Paraquat (toxicity)
• Signal Transduction