TIPE3 protects mice from lipopolysaccharide-induced acute lung injury

Background: Acute lung injury (ALI) is a severe inflammatory disease with high morbidity and mortality in pa-tients and lung transplant recipients. Tumor necrosis factor-alpha-induced protein 8-like 3 (TIPE3) is one of the members of the TIPE family. While TIPE2 has been demonstrated to be protective against lipopolysaccharide (LPS)-induced ALI, the role of TIPE3 in ALI is currently unidentified.Methods: To examine the role of TIPE3 in ALI, we pretreated C57BL/6 mice with control or TIPE3-lentivirus in LPS-induced ALI models. The C57BL/6 mice were randomly divided into four groups: control group; ALI-induced group; ALI-induced group with control lentivirus; and ALI-induced group with TIPE3-lentivirus. Additionally, RAW 264.7 cells were used to validate the role and molecular mechanism of TIPE3 signaling in vitro.Results: An increased expression of TIPE3 reduced lung histopathological damage in ALI-affected mice. ALI-affected mice treated with TIPE3-lentivirus exhibited reduced lung microvascular permeability, myeloperox-idase (MPO) activity, neutrophil buildup, and inflammation response. Additionally, over-expression of TIPE3 significantly inhibited NF-Kappa B activation and promoted the activation of Liver X receptors alpha (LXR alpha). In LPS-treated RAW264.7 cells, enforced TIPE3 expression produced anti-inflammatory effects, whereas the LXR in-hibitor geranylgeranyl pyrophosphate (GGPP) reversed these effects.Conclusions: TIPE3 protected against LPS-induced ALI by regulating the LXR alpha/NF-Kappa B signaling pathway. These results suggest that TIPE3 might provide a novel insight into the prevention of ALI.