Tuberc Respir Dis.  2003 Jul;55(1):21-30. 10.4046/trd.2003.55.1.21.

Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease

Affiliations
  • 1Division of Pulmonology, College of Medicine, Korea University, Korea. jaejshim@kumc.or.kr

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, TNFalpha was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal TNFalpha 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 TGFalpha induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently TNFalpha secretion, which was inhibited by mastoparan. LPS with TGFalpha-induced MUC5AC production was inhibited by neutralizing polyclonal TNFalpha 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 TNFalpha 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.

Keyword

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

MeSH Terms

Enzyme-Linked Immunosorbent Assay
Epidermal Growth Factor
GTP-Binding Proteins
Mucins
Mucus*
Phosphorylation
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
Receptors, G-Protein-Coupled
Signal Transduction*
Transcriptional Activation
Transforming Growth Factor alpha
Tumor Necrosis Factor-alpha
Epidermal Growth Factor
GTP-Binding Proteins
Mucins
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
Receptors, G-Protein-Coupled
Transforming Growth Factor alpha
Tumor Necrosis Factor-alpha
Full Text Links
  • TRD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error