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We utilized primary differentiated human bronchial epithelial (HBE) and A549 lung adenocarcinoma cells to further investigate the contributions of CREB and NF-\u03baB subunits to the IL-1\u03b2-induced upregulation of MUC5AC. Data show that ligand binding of IL-1\u03b2 to the IL-1\u03b2 receptor is required to increase MUC5AC mRNA abundance. Chromatin immunoprecipitation analyses show direct binding of CREB to the previously identified cAMP response element site and binding of p65 and p50 subunits to a novel NF-\u03baB site in a mucin-regulatory domain in the proximal promoter and to a previously identified NF-\u03baB site in the distal promoter. P50 binds to both NF-\u03baB sites at 1 h following IL-1\u03b2 exposure, but is replaced at 2 h by p65 in A549 cells and by a p50\/p65 heterodimer in HBE cells. Thus IL-1\u03b2 activates multiple domains in the MUC5AC promoter but exhibits some cell-specific responses, highlighting the complexity of MUC5AC transcriptional regulation. Data show that dexamethasone, a glucocorticoid that transcriptionally represses MUC5AC gene expression under constitutive conditions, also represses IL-1\u03b2-mediated upregulation of MUC5AC gene expression. A further understanding of mechanisms mediating MUC5AC regulation should lead to a honing of therapeutic approaches for the treatment of mucus overproduction in inflammatory lung diseases.<\/jats:p>","DOI":"10.1152\/ajplung.00347.2013","type":"journal-article","created":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T05:37:30Z","timestamp":1391233050000},"page":"L797-L807","source":"Crossref","is-referenced-by-count":73,"title":["IL-1\u03b2 induction of<i>MUC5AC<\/i>gene expression is mediated by CREB and NF-\u03baB and repressed by dexamethasone"],"prefix":"10.1152","volume":"306","author":[{"given":"Yajun","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Genetic Medicine Research, Children's National Health System, Washington, DC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M.","family":"Garvin","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children's National Health System, Washington, 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