High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice

Xin Wang, Renlingzi Zhang, Yao Tong, Xibing Ding, Shuqing Jin, Xiang Zhao, Jiaying Zong, Zhixia Chen, Timothy R. Billiar, Quan Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Saquinavir (SQV) is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 (TLR4)-mediated inflammatory pathway and nuclear factor-κB (NF-κB) activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1 (HMGB1) has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury (VILI). In this study, C57BL/6 mice were randomly divided into four groups (n = 10): control group and control with SQV group (Con + SQV) were spontaneous breath. HTV group (HTV) received high tidal volume ventilation (HTV) for 4 h. HTV with SQV group (HTV + SQV) were pretreated with 5 mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight (W/D) ratio, alveolar-capillary permeability to Evans blue albumin (EBA), cell counts, total proteins in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level in BALF and lung tissue, and lung histopathology were examined. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalActa Biochimica et Biophysica Sinica
Volume49
Issue number10
DOIs
StatePublished - 1 Oct 2017
Externally publishedYes

Keywords

  • HMGB1
  • NF-κB
  • Saquinavir
  • VILI
  • ventilator-induced lung injury

Fingerprint

Dive into the research topics of 'High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice'. Together they form a unique fingerprint.

Cite this