Interleukin-1β and tumor necrosis factor-α induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells

Kyoung Seob Song, Won Jae Lee, Kwang Chul chung, Ja Seok Koo, Eun Jin Yang, Jae Young Choi, Joo Heon Yoon

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

Mucin hypersecretion is commonly observed in many inflammatory diseases of the respiratory tract. MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium. Moreover, it is regulated by various inflammatory cytokines. However, the mechanisms by which the interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear. Here we show that pharmacologic or genetic inhibition of either ERK or p38 MAP kinase pathway abolished IL-1β- and TNF-α-induced MUC5AC gene expression in normal human nasal epithelial cells. Our results also indicate that the activation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-response element-binding protein and cAMP-response element signaling cascades via ERK and p38 MAP kinases are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression. Taken together, these studies give additional insights into the molecular mechanism of IL-1β- and TNF-α-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation.

Original languageEnglish
Pages (from-to)23243-23250
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number26
DOIs
Publication statusPublished - 2003 Jul 27

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MAP Kinase Kinase 1
MAP Kinase Kinase 4
p38 Mitogen-Activated Protein Kinases
Interleukin-1
Gene expression
Mucins
Tumor Necrosis Factor-alpha
Epithelial Cells
Chemical activation
Gene Expression
Nose
Respiratory Tract Diseases
Cyclic AMP Response Element-Binding Protein
Goblet Cells
Response Elements
Mitogen-Activated Protein Kinases
Epithelium
Cells
Cytokines
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Interleukin-1β and tumor necrosis factor-α induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells",
abstract = "Mucin hypersecretion is commonly observed in many inflammatory diseases of the respiratory tract. MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium. Moreover, it is regulated by various inflammatory cytokines. However, the mechanisms by which the interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear. Here we show that pharmacologic or genetic inhibition of either ERK or p38 MAP kinase pathway abolished IL-1β- and TNF-α-induced MUC5AC gene expression in normal human nasal epithelial cells. Our results also indicate that the activation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-response element-binding protein and cAMP-response element signaling cascades via ERK and p38 MAP kinases are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression. Taken together, these studies give additional insights into the molecular mechanism of IL-1β- and TNF-α-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation.",
author = "Song, {Kyoung Seob} and Lee, {Won Jae} and chung, {Kwang Chul} and Koo, {Ja Seok} and Yang, {Eun Jin} and Choi, {Jae Young} and Yoon, {Joo Heon}",
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Interleukin-1β and tumor necrosis factor-α induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. / Song, Kyoung Seob; Lee, Won Jae; chung, Kwang Chul; Koo, Ja Seok; Yang, Eun Jin; Choi, Jae Young; Yoon, Joo Heon.

In: Journal of Biological Chemistry, Vol. 278, No. 26, 27.07.2003, p. 23243-23250.

Research output: Contribution to journalArticle

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T1 - Interleukin-1β and tumor necrosis factor-α induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells

AU - Song, Kyoung Seob

AU - Lee, Won Jae

AU - chung, Kwang Chul

AU - Koo, Ja Seok

AU - Yang, Eun Jin

AU - Choi, Jae Young

AU - Yoon, Joo Heon

PY - 2003/7/27

Y1 - 2003/7/27

N2 - Mucin hypersecretion is commonly observed in many inflammatory diseases of the respiratory tract. MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium. Moreover, it is regulated by various inflammatory cytokines. However, the mechanisms by which the interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear. Here we show that pharmacologic or genetic inhibition of either ERK or p38 MAP kinase pathway abolished IL-1β- and TNF-α-induced MUC5AC gene expression in normal human nasal epithelial cells. Our results also indicate that the activation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-response element-binding protein and cAMP-response element signaling cascades via ERK and p38 MAP kinases are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression. Taken together, these studies give additional insights into the molecular mechanism of IL-1β- and TNF-α-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation.

AB - Mucin hypersecretion is commonly observed in many inflammatory diseases of the respiratory tract. MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium. Moreover, it is regulated by various inflammatory cytokines. However, the mechanisms by which the interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear. Here we show that pharmacologic or genetic inhibition of either ERK or p38 MAP kinase pathway abolished IL-1β- and TNF-α-induced MUC5AC gene expression in normal human nasal epithelial cells. Our results also indicate that the activation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-response element-binding protein and cAMP-response element signaling cascades via ERK and p38 MAP kinases are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression. Taken together, these studies give additional insights into the molecular mechanism of IL-1β- and TNF-α-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation.

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