Adenoviral E3-14.7K protein in LPS-induced lung inflammation.
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.
Harrod
K S
KS
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Mounday
A D
AD
Whitsett
J A
JA
D017503:Adenovirus E3 Proteins / Q000502:physiology; D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011510:Proteolipids / Q000235:genetics; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
D017503:Adenovirus E3 Proteins; D008070:Lipopolysaccharides; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha