Induction of MUC8 Gene Expression by Interleukin-1β Is Mediated by a Sequential ERK MAPK/RSK1/CREB Cascade Pathway in Human Airway Epithelial Cells

• Published in: The Journal of biological chemistry 2003-09, Vol.278 (37), p.34890-34896
• Main Authors: Song, Kyoung Seob, Seong, Je-Kyung, Chung, Kwang Chul, Lee, Won-Jae, Kim, Chang-Hoon, Cho, Kyou Nam, Kang, Chi-Dug, Koo, Ja Seok, Yoon, Joo-Heon
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Base Sequence; Cell Line; Cyclic AMP Response Element-Binding Protein - metabolism; DNA Primers; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; Imidazoles - pharmacology; Inflammation; Interleukin-1 - pharmacology; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mucins - genetics; Nasal Mucosa - drug effects; Nasal Mucosa - physiology; Polymerase Chain Reaction; Pyridines - pharmacology; Respiratory Mucosa - drug effects; Respiratory Mucosa - physiology; Ribosomal Protein S6 Kinases, 90-kDa - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M303911200

Mucins are the major components of the mucus layer that covers and protects the respiratory, digestive, and reproductive tracts. Our previous studies showed that MUC8 gene expression was overexpressed in in vivo polyp epithelium in chronic sinusitis and was also increased by treatment with inflammatory mediators in an in vitro culture condition. However, the mechanisms by which the inflammatory mediators-induced MUC8 gene expression in normal nasal epithelial cells evolved remain unclear. We examined the mechanism by which the important proinflammatory mediator, interleukin (IL)-1β, increases MUC8 gene expression levels. We found that pharmacologic and genetic inhibition of ERK MAPK pathway abolished IL-1β-induced MUC8 gene expression in normal human nasal epithelial cells. Moreover, the overexpression of wide-type or of the dominant-negative mutant of p90 ribosomal S6 protein kinase 1 (RSK1) enhanced or suppressed, respectively, IL-1β-induced MUC8 gene expression. RSK1 was found to directly phosphorylate cAMP-response element-binding protein (CREB), and this event led to the stimulation of subsequent CRE-mediated gene transcription. In conclusion, IL-1β was found to induce MUC8 gene expression via a sequential ERK/RSK1/CREB pathway in human airway epithelial cells.