Prostaglandin E2 induces MUC8 gene expression via a mechanism involving ERK MAPK/RSK1/cAMP response element binding protein activation in human airway epithelial cells.
MUC8 gene expression is overexpressed in nasal polyp epithelium and is also increased by treatment with inflammatory mediators in nasal epithelial cells. These data suggest that MUC8 may be one of important mucin genes expressed in human airway. However, the mechanisms of various inflammatory mediator-induced MUC8 gene expression in normal nasal epithelial cells remain unclear. We examined the mechanism by which prostaglandin E(2) (PGE2), an arachidonic acid metabolite, increases MUC8 gene expression levels. Here, we show that ERK mitogen-activated protein kinase is essential for PGE2-induced MUC8 gene expression in normal human nasal epithelial cells and that p90 ribosomal S 6 protein kinase 1 (RSK1) mediates the PGE2-induced phosphorylation of cAMP-response element binding protein. Our results also indicate that cAMP-response element at the -803 region of the MUC8 promoter is an important site of PGE2-induced MUC8 gene expression. In conclusion, this study gives insights into the molecular mechanism of PGE2-induced MUC8 gene expression in human airway epithelial cells.
Cho
Kyou-Nam
KN
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Choi
Jae Young
JY
Kim
Chang-Hoon
CH
Baek
Seung Joon
SJ
Chung
Kwang Chul
KC
Moon
Uk Yeol
UY
Kim
Kyung-Su
KS
Lee
Won-Jae
WJ
Koo
Ja Seok
JS
Yoon
Joo-Heon
JH
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System; D009077:Mucins / Q000235:genetics*; D009666:Nose / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism* / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; C105059:MUC8 protein, human; D009077:Mucins; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone