Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease

Research output: Contribution to journalArticle

Abstract

Background: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNF α was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNF α antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results: LPS alone did not increase significantly MUC5AC production. LPS with TGF α induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNF α secretion, which was inhibited by mastoparan. LPS with TGF α-induced MUC5AC production was inhibited by neutralizing polyclonal TNF a antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion: In LPS-induced MUC5AC synthesis, LPS causes TNF a secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

Original languageEnglish
Pages (from-to)21-30
Number of pages10
JournalTuberculosis and Respiratory Diseases
Volume55
Issue number1
Publication statusPublished - 2003 Jul 1

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Mucus
Lipopolysaccharides
Signal Transduction
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Transcriptional Activation
G-Protein-Coupled Receptors
Mucins
Metalloproteases
GTP-Binding Proteins
Antibodies
Enzyme-Linked Immunosorbent Assay
Matrix Metalloproteinase 7
Heterotrimeric GTP-Binding Proteins
Proteins
Neutralizing Antibodies
Matrix Metalloproteinases
Protein-Tyrosine Kinases
mastoparan
Phosphorylation

Keywords

  • Airway
  • Cell signal
  • Epidermal growth factor
  • G-protein
  • Mucin production

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease. / Shim, Jae Jeong.

In: Tuberculosis and Respiratory Diseases, Vol. 55, No. 1, 01.07.2003, p. 21-30.

Research output: Contribution to journalArticle

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abstract = "Background: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNF α was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNF α antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results: LPS alone did not increase significantly MUC5AC production. LPS with TGF α induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNF α secretion, which was inhibited by mastoparan. LPS with TGF α-induced MUC5AC production was inhibited by neutralizing polyclonal TNF a antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion: In LPS-induced MUC5AC synthesis, LPS causes TNF a secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.",
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N2 - Background: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNF α was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNF α antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results: LPS alone did not increase significantly MUC5AC production. LPS with TGF α induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNF α secretion, which was inhibited by mastoparan. LPS with TGF α-induced MUC5AC production was inhibited by neutralizing polyclonal TNF a antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion: In LPS-induced MUC5AC synthesis, LPS causes TNF a secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

AB - Background: Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method: MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, TNF α was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNF α antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results: LPS alone did not increase significantly MUC5AC production. LPS with TGF α induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNF α secretion, which was inhibited by mastoparan. LPS with TGF α-induced MUC5AC production was inhibited by neutralizing polyclonal TNF a antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion: In LPS-induced MUC5AC synthesis, LPS causes TNF a secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

KW - Airway

KW - Cell signal

KW - Epidermal growth factor

KW - G-protein

KW - Mucin production

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