Induction of MUC8 gene expression by interleukin-1β is mediated by a sequential ERK MAPK/RSK1/CREB cascade pathway in human airway epithelial cells

Kyoung Seob Song, Je Kyung Seong, Kwang Chul Chung, Won Jae Lee, Chang Hoon Kim, Kyou Nam Cho, Chi Dug Kang, Ja Seok Koo, Joo Heon Yoon

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)34890-34896
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
Publication statusPublished - 2003 Sep 12

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Ribosomal Protein S6 Kinases
Cyclic AMP Response Element-Binding Protein
Interleukin-1
Gene expression
Epithelial Cells
Gene Expression
Nose
90-kDa Ribosomal Protein S6 Kinases
MAP Kinase Signaling System
Sinusitis
Mucins
Mucus
Transcription
Polyps
Gastrointestinal Tract
Epithelium
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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. / Induction of MUC8 gene expression by interleukin-1β is mediated by a sequential ERK MAPK/RSK1/CREB cascade pathway in human airway epithelial cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 37. pp. 34890-34896.
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abstract = "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.",
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Induction of MUC8 gene expression by interleukin-1β is mediated by a sequential ERK MAPK/RSK1/CREB cascade pathway in human airway epithelial cells. / 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.

In: Journal of Biological Chemistry, Vol. 278, No. 37, 12.09.2003, p. 34890-34896.

Research output: Contribution to journalArticle

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AU - Song, Kyoung Seob

AU - Seong, Je Kyung

AU - Chung, Kwang Chul

AU - Lee, Won Jae

AU - Kim, Chang Hoon

AU - Cho, Kyou Nam

AU - Kang, Chi Dug

AU - Koo, Ja Seok

AU - Yoon, Joo Heon

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N2 - 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.

AB - 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.

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