Induction of MUC8 gene expression by interleukin-1 beta is mediated by a sequential ERK MAPK/RSK1/CREB cascade pathway in human airway epithelial cells.
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)-1 beta, increases MUC8 gene expression levels. We found that pharmacologic and genetic inhibition of ERK MAPK pathway abolished IL-1 beta-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-1 beta-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-1 beta was found to induce MUC8 gene expression via a sequential ERK/RSK1/CREB pathway in human airway epithelial cells.
Song
Kyoung Seob
KS
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Seong
Je-Kyung
JK
Chung
Kwang Chul
KC
Lee
Won-Jae
WJ
Kim
Chang-Hoon
CH
Cho
Kyou Nam
KN
Kang
Chi-Dug
CD
Koo
Ja Seok
JS
Yoon
Joo-Heon
JH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009077:Mucins / Q000235:genetics*; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D007093:Imidazoles; D007375:Interleukin-1; C105059:MUC8 protein, human; D009077:Mucins; D011725:Pyridines; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C093642:SB 203580