Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/9154230 |
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| author | Qin Wang Jianchun Wang Mingdong Hu Yu Yang Liang Guo Jing Xu Chuanjiang Lei Yan Jiao JianCheng Xu |
| author_facet | Qin Wang Jianchun Wang Mingdong Hu Yu Yang Liang Guo Jing Xu Chuanjiang Lei Yan Jiao JianCheng Xu |
| author_sort | Qin Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ed7fc12b513f45b7af840e6d30f26f6f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-ed7fc12b513f45b7af840e6d30f26f6f2025-02-03T06:14:09ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/91542309154230Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in MiceQin Wang0Jianchun Wang1Mingdong Hu2Yu Yang3Liang Guo4Jing Xu5Chuanjiang Lei6Yan Jiao7JianCheng Xu8Department of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaDepartment of Pneumology, Xinqiao Hospital, The Third Military Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing 400037, ChinaUncoupling 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.http://dx.doi.org/10.1155/2016/9154230 |
| spellingShingle | Qin Wang Jianchun Wang Mingdong Hu Yu Yang Liang Guo Jing Xu Chuanjiang Lei Yan Jiao JianCheng Xu Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice Mediators of Inflammation |
| title | Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| title_full | Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| title_fullStr | Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| title_full_unstemmed | Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| title_short | Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| title_sort | uncoupling protein 2 increases susceptibility to lipopolysaccharide induced acute lung injury in mice |
| url | http://dx.doi.org/10.1155/2016/9154230 |
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