Epigallocatechin Gallate Attenuates Mitochondrial DNA-induced Inflammatory Damage in the Development of Ventilator-induced Lung Injury

Jia Hu, CHAO-YI QIN, PENG YANG, YAO HUANG, ZHENG-HUA XIAO, ER-YONG ZHANG

West China Hospital, Si Chuan University, China, ChengDu, China

Date, time and location: 2018.05.26 13:30, Press Hall, 2F

Abstract

Objective: We aim to investigate the role of mitochondrial DNA (mtDNA) in the development of ventilator-induced lung injury (VILI). Moreover, the protective effect of epigallocatechin gallate (EGCG) on VILI through inhibiting local mtDNA release was examined.

Methods: Thirty-six patients with VILI and well-matched 36 patients without VILI after major non-cardiac surgery were consecutively enrolled. Bronchoaveolar lavage fluid (BALF) of all patients was collected . SD rats were divided into five groups: control, low tidal volume (7ml/Kg) group, high tidal volume (HTV, 40ml/Kg) group, HTV+ low dose EGCG and HTV + high dose EGCG groups.  In addition, cyclic stretch cell culture was used and culture media was collected to analyze expressions of inflammatory cytokines. Administration of mtDNA in a rat model and in vitro cell culturing were also used. 

Results: A Significant elevation of mtDNA was detected in BALF from VILI patients (581 ± 193 vs. 311 ± 137, p < 0.05) and also in rats ventilated with HTV. EGCG could significantly inhibit HTV-induced local mtDNA release and attenuate inflammatory lung injuries . The beneficial effects of EGCG  were in a concentration-dependent manner.  Higher expression levels of mtDNA and inflammatory cytokines were observed in the media of cyclic stretched cell culture . Furthermore, intra-tracheal administration of mtDNA in rats could lead to a marked increase of local inflammatory cytokines and subsequent inflammatory lung injuries . And by adding mtDNA into cell culture, higher level of inflammatory cytokines in the media was detected (p < 0.05). EGCG showed suppressive effects on inflammatory responses in a concentration-dependent manner (p < 0.05).

Conclusions: The increased expression level of mtDNA and subsequent inflammatory cytokines overproduction may play an important role in the development of VILI. EGCG may be a potential novel therapeutic candidate for protection against VILI by inhibiting the local release of mtDNA