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Inhalation Toxicology
International Forum for Respiratory Research
Volume 30, 2018 - Issue 4-5
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Research Article

Adenovirus-delivered angiopoietin-1 ameliorates phosgene-induced acute lung injury via inhibition of NLRP3 inflammasome activation

Dai-Kun HeCenter of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Research Centre for Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
,
Jun-Feng ChenCenter of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Research Centre for Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
,
Yi-Ru ShaoCenter of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Research Centre for Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, ChinaORCID Iconhttp://orcid.org/0000-0002-6593-6761View further author information
ORCID Icon,
Fang-Qing ZhouCenter of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Research Centre for Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
&
Jie ShenCenter of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; ;Medical Research Centre for Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, ChinaCorrespondence[email protected]
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Pages 187-194 | Received 27 Jan 2018, Accepted 20 Jun 2018, Published online: 26 Sep 2018
 
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Abstract

Objective: Angiopoietin-1 (Ang1) is reported to have the ability to attenuate endothelial permeability and inflammation during the stress condition and is considered to play a critical role in vascular stabilization. The aim of this study was to investigate the mechanisms involved in the protective effects of adenovirus-delivered Ang1 in phosgene-induced acute lung injury (ALI).

Methods: ALI was induced in rats by phosgene exposure at 8.33 g/m3 for 5 min, followed by an intravenous injection of adenovirus-Ang1 (Ad/Ang1). The histologic changes of the lung were evaluated with H&E staining. The levels of cytokines in the serum and bronchoalveolar lavage fluid (BALF) were determined by ELISA. NLRP3 inflammasome activation was assessed with immunohistochemistry, RT-PCR, Western blotting and TUNEL staining.

Results: Histologic analyses suggested that reduced severity in phosgene-induced ALI with Ad/Ang1 treatment. Reduced levels of IL-1β, IL-18 and IL-33 were found in both serum and BALF samples from Ad/Ang1-treated ALI rats induced by phosgene. Moreover, immunohistochemistry analysis revealed that Ad/Ang1 treatment inhibited the NLRP3 inflammasome activation. Decreased mRNA and protein levels of NLRP3 and caspase-1 were found in phosgene-exposed rats treated with Ad/Ang1. In addition, TUNEL staining indicated a decrease in pyroptosis in phosgene-exposed rats treated with Ad/Ang1.

Conclusions: Ang1 exerts beneficial effects on phosgene-induced lung injury via inhibition of NLRP3 inflammasome activation. Disruption of NLRP3 inflammasome activation might be served as therapeutic modality for the treatment of phosgene-induced ALI.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by Research Project of Shanghai municipal health and Family Planning Commission [No. 201540192] to D.K.H., National Youth Nature Science Foundation of China [No. 81101412] to D.K.H. and National Natural Science Foundation of China [No. 81471850] to S.J.

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