Human airway epithelial cell lines that retain phenotypic properties representative of the native tissue will be useful physiological models. Human papilloma viral (HPV) genes can immortalize human genital keratinocytes and breast and bronchial epithelia. We transfected cystic fibrosis (CF) and normal tracheobronchial epithelial cell cultures with DNA encoding the HPV-18 E6 and E7 genes and characterized phenotypic properties of resultant cell lines. Of the 11 CF clones isolated, 6 developed a polarized phenotype with vectorial ion transport and membrane-specific expression of histamine and purinergic receptors. The ion transport properties of these lines differed from the normal lines and approximated those of primary CF airway epithelial cell cultures more closely than do those of cell lines transformed with the simian virus 40 large T gene. When transplanted into denuded tracheal grafts, these cells can differentiate into ciliated and secretory phenotypes. We conclude that HPV-18 E6 and E7 genes are sufficient to transform human airway epithelial cells and that the resultant cell lines express differentiated phenotypic properties that approximate those of the native epithelium.
One of the most challenging issues of anti-inflammatory lines. In conditionally immortalized human endometrial gene therapy is the complexity of inflammatory pathways.stromal cells, overexpression of IB␣ prevented both Transcription factor NF-B plays a pivotal role in activation interleukin-1 (IL-1)-inducible degradation of endogenous of multiple inflammatory molecules, and therefore rep-IB␣ protein and activation of NF-B. Accordingly, inducresents the logical target for intervention. We evaluated the tion of cytokines interleukin-8 (IL-8) and Gro␥ was markfeasibility of suppressing the inflammatory responses in difedly suppressed. In monocytic THP-1 cells, both lipopolyferent cell lines through specific inhibition of NF-B by gene saccharide (
We have developed methods for the culture of human endometrial glandular epithelia in vitro. The culture medium is serum-free and is used in combination with Matrigel, an extracellular matrix material applied as a coating on cell culture plates. Cell growth begins as a monolayer, but the cells subsequently form glandular or organoid structures. The glands are composed of polar columnar cells facing a central lumen, which is enclosed by the apical surfaces of cells displaying numerous microvilli and sealed by tight junction complexes. The ability to study in vitro the complex process of glandular morphogenesis represents an important new tool in cell biology which may be used to investigate growth regulation, hormone production and dependency, and cellular recognition and interactions. Ultimately, these characteristics may be applied to study the alterations of glandular epithelia associated with neoplasia.
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