Abstract
It has been reported that DOK3 protein negatively regulates LPS responses and endotoxin tolerance in mice. However, the role of DOK3 in the development of acute respiratory distress syndrome (ARDS) remains unknown. In this study, we showed that DOK3 is degraded in the lung tissues of LPS-induced ARDS. Through lentivirus transduction containing DOK3(K27R) via the intranasal route, we created a mice model, in which DOK3 maintains stable expression. We found that the forced DOK3 expression significantly attenuated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNFα, IL- 1β and IL-6 in BALF of LPS-induced ARDS mice. In addition, DOK3 expression apparently suppressed LPS-induced NF-κB and ERK activation. These data suggested that DOK3 expression negatively regulates the development of LPS-induced ARDS in mice.
Keywords: ARDS, DOK3, Lentivirus, LPS, Degradation, Expression.
Current Gene Therapy
Title:DOK3 Degradation is Required for the Development of LPS-induced ARDS in Mice
Volume: 16 Issue: 4
Author(s): Ning Liu, Xiaofeng Liu, Xiaoou Li, Kaifang Duan, Yuming Deng, Xiuyan Yu and Qisheng Peng
Affiliation:
Keywords: ARDS, DOK3, Lentivirus, LPS, Degradation, Expression.
Abstract: It has been reported that DOK3 protein negatively regulates LPS responses and endotoxin tolerance in mice. However, the role of DOK3 in the development of acute respiratory distress syndrome (ARDS) remains unknown. In this study, we showed that DOK3 is degraded in the lung tissues of LPS-induced ARDS. Through lentivirus transduction containing DOK3(K27R) via the intranasal route, we created a mice model, in which DOK3 maintains stable expression. We found that the forced DOK3 expression significantly attenuated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNFα, IL- 1β and IL-6 in BALF of LPS-induced ARDS mice. In addition, DOK3 expression apparently suppressed LPS-induced NF-κB and ERK activation. These data suggested that DOK3 expression negatively regulates the development of LPS-induced ARDS in mice.
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Liu Ning, Liu Xiaofeng, Li Xiaoou, Duan Kaifang, Deng Yuming, Yu Xiuyan and Peng Qisheng, DOK3 Degradation is Required for the Development of LPS-induced ARDS in Mice, Current Gene Therapy 2016; 16 (4) . https://dx.doi.org/10.2174/1566523216666161103142342
DOI https://dx.doi.org/10.2174/1566523216666161103142342 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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