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Upregulation of MUC5AC gene expression by IL-4 through CREB in human airway epithelial cells

Authors
 Cheol Hong Kim  ;  Kyu-Earn Kim  ;  Joo-Heon Yoon  ;  Kyoung Seob Song 
Citation
 JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.108(4) : 974-981, 2009 
Journal Title
 JOURNAL OF CELLULAR BIOCHEMISTRY 
ISSN
 0730-2312 
Issue Date
2009
MeSH
Cell Line, Tumor ; Cyclic AMP/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Epithelial Cells/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Flavonoids/pharmacology ; Gene Expression Regulation* ; Humans ; Interleukin-4/metabolism* ; Mucin 5AC/biosynthesis* ; Phosphorylation ; Response Elements/genetics ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
allergen ; asthma ; IL‐4 ; MUC5AC ; CREB
Abstract
Mucus hypersecretion is an important characteristic feature of the pathogenesis of allergy. Although interleukin (IL)-4 is known to be an inflammatory mediator in respiratory diseases, the mechanism by which IL-4 induces MUC5AC gene expression has not been fully explored. The aim of this study was to investigate the mechanism by which IL-4 induces MUC5AC gene expression in the airway. We examined the role of mitogen-activated protein kinase (MAPK) signaling on MUC5AC gene expression in airway epithelium. We showed that phosphorylation of ERK1/2 increased after treatment of cells with IL-4, whereas phosphorylation of p38 and JNK was not detected. In addition, pharmacologic and genetic inhibition of ERK1/2 abolished IL-4-induced MUC5AC gene expression. Moreover, we investigated the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in IL-4 signaling. The activation of RSK1 was prevented by pretreatment with PD98059 or plasmid expressing a MEK1 dominant-negative mutant. We also found that RSK1 mediated the IL-4-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the MUC5AC promoter appears to be important for IL-4-induced MUC5AC gene expression in NCI-H292 cells.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/jcb.22330/abstract
DOI
10.1002/jcb.22330
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyu Earn(김규언)
Yoon, Joo Heon(윤주헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105590
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