Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in MiceReport as inadecuate




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Mediators of Inflammation - Volume 2016 2016, Article ID 9154230, 13 pages -

Research ArticleDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, China

Received 15 August 2015; Revised 14 December 2015; Accepted 6 January 2016

Academic Editor: Stefanie B. Flohé

Copyright © 2016 Qin Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Uncoupling protein 2 UCP2 is upregulated in patients with systemic inflammation and infection, but its functional role is unclear. We up- or downregulated UCP2 expression using UCP2 recombinant adenovirus or the UCP2 inhibitor, genipin, in lungs of mice, and investigated the mechanisms of UCP2 in ALI. UCP2 overexpression in mouse lungs increased LPS-induced pathological changes, lung permeability, lung inflammation, and lowered survival rates. Furthermore, ATP levels and mitochondrial membrane potential were decreased, while reactive oxygen species production was increased. Additionally, mitogen-activated protein kinases MAPKs activity was elevated, which increased the sensitivity to LPS-induced apoptosis and inflammation. LPS-induced apoptosis and release of inflammatory factors were alleviated by pretreatment of the Jun N-terminal kinase JNK inhibitor SP600125 or the p38 MAPK inhibitor SB203580, but not by the extracellular signal-regulated kinase ERK inhibitor PD98059 in UCP2-overexpressing mice. On the other hand, LPS-induced alveolar epithelial cell death and inflammation were attenuated by genipin. In conclusion, UCP2 increased susceptibility to LPS-induced cell death and pulmonary inflammation, most likely via ATP depletion and activation of MAPK signaling following ALI in mice.





Author: Qin Wang, Jianchun Wang, Mingdong Hu, Yu Yang, Liang Guo, Jing Xu, Chuanjiang Lei, Yan Jiao, and JianCheng Xu

Source: https://www.hindawi.com/



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