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Adenoviral E3-14.7K protein in LPS-induced lung inflammation
K S Harrod1, A D Mounday, J A Whitsett
1Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Abstract:
The adenoviral E3-14.7K protein is a cytoplasmic protein synthesized after adenoviral infection. To assess the contribution of E3-14. 7K-sensitive pathways in the modulation of inflammation by the respiratory epithelium, inflammatory responses to intratracheal lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha were assessed in transgenic mice bearing the adenoviral E3-14.7K gene under the direction of the surfactant protein (SP) C promoter. When E3-14.7K transgenic mice were administered LPS intratracheally, lung inflammation as indicated by macrophage and neutrophil accumulation in bronchoalveolar lavage fluid was decreased compared with wild-type control mice. Lung inflammation and epithelial cell injury were decreased in E3-14.7K mice 24 and 48 h after LPS administration. Intracellular staining for surfactant proprotein (proSP) B, proSP-C, and SP-B was decreased and extracellular staining was markedly increased in wild-type mice after LPS administration, consistent with LPS-induced lung injury. In contrast, intense intracellular staining of proSP-B, proSP-C, and SP-B persisted in type II cells of E3-14.7K mice, whereas extracellular staining of proSP-B and proSP-C was absent. Inhibitory effects of intratracheal LPS on SP-C mRNA were ameliorated by expression of the E3-14.7K gene. Similar to the response to LPS, lung inflammation after intratracheal administration of TNF-alpha was decreased in E3-14.7K transgenic mice. Levels of TNF-alpha after LPS administration were similar in wild-type and E3-14.7K-bearing mice. Cell-selective expression of E3-14.7K in the respiratory epithelium inhibited LPS- and TNF-alpha-mediated lung inflammation, demonstrating the critical role of respiratory epithelial cells in LPS- and TNF-alpha-induced lung inflammation.
Insights
Adenoviral E3-14.7K protein expression in respiratory epithelium reduces lung inflammation caused by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha). This highlights the epithelial cells' crucial role in inflammatory responses.
Area of Science:
- Molecular biology
- Immunology
- Respiratory medicine
Background:
- The adenoviral E3-14.7K protein is a cytoplasmic protein synthesized post-adenoviral infection.
- Respiratory epithelial cells play a role in modulating inflammation.
- Adenoviral E3-14.7K protein's role in inflammation is not fully understood.
Purpose of the Study:
- To assess the contribution of E3-14.7K-sensitive pathways in the respiratory epithelium to inflammation modulation.
- To investigate the impact of adenoviral E3-14.7K protein on lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) induced lung inflammation.
Main Methods:
- Transgenic mice expressing adenoviral E3-14.7K gene under the surfactant protein (SP) C promoter were used.
- Mice were administered LPS or TNF-alpha intratracheally.
- Lung inflammation was assessed by macrophage and neutrophil accumulation in bronchoalveolar lavage fluid.
- Epithelial cell injury and surfactant protein expression were evaluated.
Main Results:
- E3-14.7K transgenic mice showed decreased lung inflammation and epithelial cell injury after LPS administration compared to wild-type mice.
- Intracellular surfactant proprotein (proSP) B, proSP-C, and SP-B staining persisted in E3-14.7K mice, while extracellular staining was absent.
- Expression of E3-14.7K ameliorated LPS-induced inhibition of SP-C mRNA.
- Lung inflammation induced by TNF-alpha was also decreased in E3-14.7K transgenic mice.
Conclusions:
- Cell-selective expression of E3-14.7K in the respiratory epithelium inhibits LPS- and TNF-alpha-mediated lung inflammation.
- Respiratory epithelial cells play a critical role in LPS- and TNF-alpha-induced lung inflammation.
- The adenoviral E3-14.7K protein modulates inflammatory responses in the respiratory tract.