DOK3 Degradation is Required for the Development of LPS-induced ARDS in Mice

Curr Gene Ther. 2016;16(4):256-262. doi: 10.2174/1566523216666161103142342.

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; Degradation; Expression; LPS; Lentivirus.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • HEK293 Cells
  • Humans
  • Lipopolysaccharides / toxicity
  • Lung / metabolism
  • Lung / pathology*
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Peroxidase / metabolism
  • Proteolysis
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / metabolism
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Dok3 protein, mouse
  • Lipopolysaccharides
  • NF-kappa B
  • Peroxidase
  • Extracellular Signal-Regulated MAP Kinases