{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T22:39:49Z","timestamp":1721687989549},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2010,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucins are high molecular weight proteins that make up the major components of mucus. Hypersecretion of mucus is a feature of several chronic inflammatory airway diseases. <jats:italic>MUC8<\/jats:italic> is an important component of airway mucus, and its gene expression is upregulated in nasal polyp epithelium. Little is known about the molecular mechanisms of <jats:italic>MUC8<\/jats:italic> gene expression. We first observed overexpression of activator protein\u20102alpha (AP2\u03b1) in human nasal polyp epithelium. We hypothesized that AP2\u03b1 overexpression in nasal polyp epithelium correlates closely with <jats:italic>MUC8<\/jats:italic> gene expression. We demonstrated that phorbol 12\u2010myristate 13\u2010acetate (PMA) treatment of the airway epithelial cell line NCI\u2010H292 increases <jats:italic>MUC8<\/jats:italic> gene and AP2\u03b1 expression. In this study, we sought to determine which signal pathway is involved in PMA\u2010induced <jats:italic>MUC8<\/jats:italic> gene expression. The results show that the protein kinase C and mitogen\u2010activating protein\/ERK kinase (MAPK) pathways modulate <jats:italic>MUC8<\/jats:italic> gene expression. PD98059 or ERK1\/2 siRNA and RO\u201031\u20108220 or PKC siRNA significantly suppress AP2\u03b1 as well as <jats:italic>MUC8<\/jats:italic> gene expression in PMA\u2010treated cells. To verify the role of AP2\u03b1, we specifically knocked down AP2\u03b1 expression with siRNA. A significant AP2\u03b1 knock\u2010down inhibited PMA\u2010induced <jats:italic>MUC8<\/jats:italic> gene expression. While dominant negative AP2\u03b1 decreased PMA\u2010induced <jats:italic>MUC8<\/jats:italic> gene expression, overexpressing wildtype AP2\u03b1 increased <jats:italic>MUC8<\/jats:italic> gene expression. Furthermore, using lentiviral vectors for RNA interference in human nasal polyp epithelial cells, we confirmed an essential role for AP2\u03b1 in <jats:italic>MUC8<\/jats:italic> gene expression. From these results, we concluded that PMA induces <jats:italic>MUC8<\/jats:italic> gene expression through a mechanism involving PKC, ERK1\/2, and AP2\u03b1 activation in human airway epithelial cells. J. Cell. 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