{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:52:57Z","timestamp":1791733977658,"version":"4.3.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mucin over-production is one of the hallmarks of chronic airway diseases such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. NF-\u03baB activation in airway epithelial cells has been shown to play a positive inflammatory role in chronic airway diseases; however, the role of NF-\u03baB in mucin gene expression is unresolved. In this study, we have shown that the proinflammatory cytokines, IL-1\u03b2 and IL-17A, both of which utilize the NF-\u03baB pathway, are potent inducers of mucin (MUC)5AC mRNA and protein synthesis by both well-differentiated primary normal human bronchial epithelial cells and the human bronchial epithelial cell line, HBE1. MUC5AC induction by these cytokines was both time- and dose-dependent and occurred at the level of promoter activation, as measured by a reporter gene assay. These effects were attenuated by the small molecule inhibitor NF-\u03baB inhibitor III, as well as p65 small-interfering RNA, suggesting that the regulation of MUC5AC expression by these cytokines is via an NF-\u03baB-based transcriptional mechanism. Further investigation of the promoter region identified a putative NF-\u03baB binding site at position-3594\/-3582 in the promoter of MUC5AC as critical for the regulation of MUC5AC expression by both IL-1\u03b2 and IL-17A. Chromatin immunoprecipitation analysis confirmed enhanced binding of the NF-\u03baB subunit p50 to this region following cytokine stimulation. We conclude that an NF-\u03baB-based transcriptional mechanism is involved in MUC5AC regulation by IL-1\u03b2 and IL-17A in the airway epithelium. This is the first demonstration of the participation of NF-\u03baB and its specific binding site in cytokine-mediated airway MUC5AC expression.<\/jats:p>","DOI":"10.4049\/jimmunol.0900614","type":"journal-article","created":{"date-parts":[[2009,10,19]],"date-time":"2009-10-19T21:31:56Z","timestamp":1255987916000},"page":"6236-6243","source":"Crossref","is-referenced-by-count":238,"title":["Regulation of Airway\n                    <i>MUC5AC<\/i>\n                    Expression by IL-1\u03b2 and IL-17A; the NF-\u03baB Paradigm"],"prefix":"10.1093","volume":"183","author":[{"given":"Tomoyuki","family":"Fujisawa","sequence":"first","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlene","family":"Velichko","sequence":"additional","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Thai","sequence":"additional","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yin","family":"Hung","sequence":"additional","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Huang","sequence":"additional","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reen","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Comparative Respiratory Biology and Medicine, University of California , Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,11,15]]},"reference":[{"key":"2025032603214322600_R1","first-page":"571","article-title":"Mucus clearance as a primary innate defense mechanism for mammalian airways.","volume-title":"J. 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