The human MUC7 gene encodes a low molecular mass mucin glycoprotein that functions in modulation of microbial flora in the oral cavity and respiratory tracts. MUC7 gene expression is tissue- and cell-specific with dominant expression in salivary gland acinar cells. To begin to understand the molecular mechanisms responsible for controlling MUC7 gene expression, we have analyzed the promoter activity of MUC7 5'-flanking region in a human lung epithelial cell line A549. We have demonstrated that MUC7 gene is expressed constitutively in this cell line and is up-regulated by TNF--stimulation. The promoter activities of a 2762 bp fragment of the human genomic DNA (-2732/+30 bp) and its deletion series, subcloned into a luciferase reporter vector, were characterized at the basal level and under stimulation by TNF-. The results indicated that the minimal functional MUC7 promoter is in the region of -138/+30 bp. This region also revealed the greatest increase in the promoter activity upon TNF--stimulation. Two putative AP1 binding elements and one NF-B binding element were identified within the proximal promoter. Further analyses demonstrated that mutations of these elements dramatically reduced specific DNA-protein binding ability and reporter gene expression, and that the two AP1 elements played an essential role in the constitutive expression, while the NF-B element was crucially important in the response to TNF--stimulation.