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TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury

  • Xiaojing Wu
  • Qian Kong
  • Liying Zhan
  • Zhen Qiu
  • Qin Huang
  • Xuemin SongEmail author
Original Research Paper

Abstract

Objective

Tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) has strong anti-inflammatory properties. However, it is unknown whether increased TIPE2 is protective against lipopolysaccharide (LPS)-induced ALI. In the current study, we aimed to investigate whether increased TIPE2 can exert protective effects in a mouse model of ALI induced by LPS.

Methods

We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Three weeks later, ALI was induced by intratracheal injection of LPS into BALB/c mice. Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression.

Results

We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. Moreover, TIPE2 overexpression markedly attenuated lung inflammation, as evidenced by the downregulation of polymorphonuclear neutrophils (PMNs) in the BALF, lung MPO activity, and pro-inflammatory cytokine levels in the serum. Moreover, TIPE2 overexpression not only dramatically prevented LPS-induced pulmonary cell apoptosis in mice but also blocked LPS-activated JNK phosphorylation and NF-κB p65 nuclear translocation.

Conclusions

Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-κB and JNK in a murine model of ALI.

Keywords

Acute lung injury TIPE2 Apoptosis Inflammation Cytokines NF-κB JNK 

Abbreviations

ALI

Acute lung injury

ARDS

Acute respiratory distress syndrome

BALF

Bronchoalveolar lavage fluid

ELISA

Enzyme-linked immunosorbent assay

i.t.

Intratracheal

LPS

Lipopolysaccharide

MPO

Myeloperoxidase

PBS

Phosphate-buffered saline

PMNs

Polymorphonuclear neutrophils

TUNEL

Deoxynucleotidyl transferase dUTP nick end labeling

W/D

Wet-to-dry

TIPE2

Tumor necrosis factor-α-induced protein 8-like 2

Notes

Acknowledgements

This work was supported by research grants from the National Natural Science Foundation of China (no. 81571941).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Xiaojing Wu
    • 1
  • Qian Kong
    • 1
  • Liying Zhan
    • 1
  • Zhen Qiu
    • 1
  • Qin Huang
    • 1
  • Xuemin Song
    • 2
    Email author
  1. 1.Department of AnesthesiologyRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Anesthesiology and Critical Care MedicineZhongnan Hospital of Wuhan UniversityWuhanChina

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