Published ahead of print on March 2, 2006, doi:10.1165/rcmb.2005-0305OC
American Journal of Respiratory Cell and Molecular Biology. Vol. 35, pp. 95-102, 2006
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0305OC
Modulation of MUC7 Mucin Expression by Exogenous Factors in Airway Cells In Vitro and In Vivo
Shimin Li,
Giuseppe Intini and
Libuse A. Bobek
Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, New York
The human MUC7 gene encodes a low-molecular-mass mucin that participates in the maintenance of healthy epithelium in the oral cavity, and possibly in respiratory tracts, by promoting the clearance of various bacteria. We examined whether MUC7 gene is expressed in primary normal human tracheobronchial epithelial cells and whether the expression is modulated by exogenous factors. By assessing MUC7 transcripts, we found that the MUC7 gene was induced by culturing the normal human tracheobronchial epithelial cells at the airliquid interface, in which the cells were well differentiated. When the cells were treated with a panel of cytokines (IL-1 , IL-4, IL-13, and TNF- ), epidermal growth factor, or a bacterial product (Pseudomonas aeruginosa lipopolysaccharide [LPS]), MUC7 transcripts and glycoprotein products were increased 1.7- to 3.2-fold. The effect of LPS on MUC7 gene expression was also studied in the airway tissues of MUC7 gene transgenic mice. In the in vitro cultured trachea and lung explants, the LPS-treated tissues showed over 2-fold increased levels of MUC7 mRNA compared with the untreated specimens. These results were confirmed by in vivo studies using the lungs and tracheas harvested from the transgenic mice irritated by LPS through the tracheal instillation. By immunohistochemistry, MUC7 glycoprotein was localized in tracheal submucosa within the serous cells. Upon LPS stimulation, the overexpressed MUC7 remains confined to the serous glands. In the lungs, MUC7 seems to be expressed within the respiratory epithelium at the level of the bronchioles. Upon stimulation with LPS, it seems to be overexpressed within the same cells and within the stromal tissue.
Key Words: intratracheal instillation immunohistochemistry MUC7 gene expression and regulation MUC7 gene transgenic mice real-time PCR tracheobronchial epithelial cells
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Copyright © 2006 American Thoracic Society.
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