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. The present study first examined whether MUC7 gene is expressed in primary normal human tracheobronchial epithelial (NHTBE) 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 NHTBE cells at air-liquid interface (ALI), in which the cells were well-differentiated. When the cells were treated with a panel of cytokines (IL-1, IL-4, IL-13, TNF-), a growth factor (EGF) and a bacterial product (Pseudomonas aeruginosa 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 to 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 sub-mucosa within the serous cells. Upon LPS stimulation, the over-expressed MUC7 remains confined to the serous glands. In the lungs, MUC7 appears to be expressed within the respiratory epithelium at the level of the bronchioles. Upon stimulation with LPS, it appears over-expressed within the same cells and within the stromal tissue.