The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling

Yeon Ho Choi, Sang Nam Lee, Hiroki Aoyagi, Yasundo Yamasaki, Jung Yoon Yoo, Boryung Park, DongMin Shin, Ho Geun Yoon, Joo Heon Yoon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS).PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2-induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2-induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2+ did not have such an effect. PGD 2-induced MUC5BmRNAlevels were regulated by CREB via direct interaction with two cAMP-response element sites (-921/-914 and -900/-893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.

Original languageEnglish
Pages (from-to)34199-34214
Number of pages16
JournalJournal of Biological Chemistry
Volume286
Issue number39
DOIs
Publication statusPublished - 2011 Oct 30

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Ribosomal Protein S6 Kinases
Prostaglandins D
Cyclic AMP Response Element-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
Gene expression
Prostaglandins
Gene Expression
prostaglandin R2 D-isomerase
Epithelial Cells
7(2-(5-hydroxybenzo(b)thiophen-3-ylcarbonylamino)-10-norpinan-3-yl)hept-5-enoic acid
Mucins
Nose
Formyl Peptide Receptor
Nasal Polyps
Prostaglandin D2
Pulmonary diseases
Th2 Cells
Mitogen-Activated Protein Kinase 1
Response Elements

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{99a4020bd8074d9584e9ae02ed8cad3f,
title = "The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling",
abstract = "Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS).PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2-induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2-induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2+ did not have such an effect. PGD 2-induced MUC5BmRNAlevels were regulated by CREB via direct interaction with two cAMP-response element sites (-921/-914 and -900/-893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.",
author = "Choi, {Yeon Ho} and Lee, {Sang Nam} and Hiroki Aoyagi and Yasundo Yamasaki and Yoo, {Jung Yoon} and Boryung Park and DongMin Shin and Yoon, {Ho Geun} and Yoon, {Joo Heon}",
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The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling. / Choi, Yeon Ho; Lee, Sang Nam; Aoyagi, Hiroki; Yamasaki, Yasundo; Yoo, Jung Yoon; Park, Boryung; Shin, DongMin; Yoon, Ho Geun; Yoon, Joo Heon.

In: Journal of Biological Chemistry, Vol. 286, No. 39, 30.10.2011, p. 34199-34214.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling

AU - Choi, Yeon Ho

AU - Lee, Sang Nam

AU - Aoyagi, Hiroki

AU - Yamasaki, Yasundo

AU - Yoo, Jung Yoon

AU - Park, Boryung

AU - Shin, DongMin

AU - Yoon, Ho Geun

AU - Yoon, Joo Heon

PY - 2011/10/30

Y1 - 2011/10/30

N2 - Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS).PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2-induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2-induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2+ did not have such an effect. PGD 2-induced MUC5BmRNAlevels were regulated by CREB via direct interaction with two cAMP-response element sites (-921/-914 and -900/-893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.

AB - Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS).PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2-induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2-induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2+ did not have such an effect. PGD 2-induced MUC5BmRNAlevels were regulated by CREB via direct interaction with two cAMP-response element sites (-921/-914 and -900/-893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.

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