The dysfunction of alveolar barriers is a critical factor in the development of lung injury and subsequent fibrosis, but the underlying molecular mechanisms remain poorly understood. To clarify the pathogenic roles of tight junctions in lung injury and fibrosis, we examined the altered expression of claudins, the major components of tight junctions, in the lungs of disease models with pulmonary...

Many organs consist of a hollow cavity surrounded by a monolayer of epithelial cells. Despite their common structure, such organs form by diverse morphogenetic processes. Three-dimensional culture systems have been useful in analyzing the events. Most processes require a combination of cell proliferation and cell death to produce a hollow cavity. Here, we describe a new three-dimensional cultur...

BACKGROUND Respiratory syncytial virus (RSV) is associated with wheezing illness, and infections can occur repeatedly throughout life. We hypothesized that RSV infection of respiratory tract epithelial cells up-regulates B7 molecules that regulate memory immune responses and that type 1 and 2 cytokines differentially modulate this induction. METHODS We used flow-cytometric analysis to investi...

Nuclear erythroid-related factor 2 (Nrf2), a redox-sensitive transcription factor, is involved in transcriptional regulation of many antioxidant genes, including glutamate-cysteine ligase (GCL). Cigarette smoke (CS) is known to cause oxidative stress and deplete glutathione (GSH) levels in alveolar epithelial cells. We hypothesized that resveratrol, a polyphenolic phytoalexin, has antioxidant s...

Many organs consist of a hollow cavity surrounded by a monolayer of epithelial cells. Despite their common structure, such organs form by diverse morphogenetic processes. Three-dimensional culture systems have been useful in analyzing the events. Most processes require a combination of cell proliferation and cell death to produce a hollow cavity. Here, we describe a new three-dimensional cultur...

Sorting nexin 5 (Snx5) has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 ...

Christ-Crain and colleagues [1] established in their work a close relationship between pro-adrenomedullin levels and severity of community acquired pneumonia. This raises the question of whether this peptide or its precursor adrenomedullin are involved in the pathogenesis of the respiratory compromise in pneumonia. Adrenomedullin induces nitric oxide (NO) production in endothelial cells through...

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT ...

Intra-alveolar fibrin deposition is a common response to localized and diffuse lung infection and acute lung injury (ALI). We hypothesized that the alveolar epithelium modulates intra-alveolar fibrin deposition through activation of protein C. Our objectives [corrected] were to determine whether components of the protein C activation pathway are present in the alveolar compartment in ALI and wh...

Hussein O, Walters B, Stroetz R, Valencia P, McCall D, Hubmayr RD. Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 305: L478–L484, 2013. First published August 30, 2013; doi:10.1152/ajplung.00437.2012.—Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone ...