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.
