Tuberc Respir Dis > Volume 55(1); 2003 > Article
Tuberculosis and Respiratory Diseases 2003;55(1):21-30.
DOI: https://doi.org/10.4046/trd.2003.55.1.21    Published online July 1, 2003.
Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease.
Jae Jeong Shim
Division 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.
Key Words: Airway, Mucin production, Epidermal growth factor, Cell signal, G-protein
TOOLS
METRICS Graph View
  • 4 Crossref
  •   Scopus
  • 992 View
  • 15 Download
Related articles


ABOUT
ARTICLE & TOPICS
Article category

Browse all articles >

Topics

Browse all articles >

BROWSE ARTICLES
FOR CONTRIBUTORS
Editorial Office
101-605, 58, Banpo-daero, Seocho-gu (Seocho-dong, Seocho Art-Xi), Seoul 06652, Korea
Tel: +82-2-575-3825, +82-2-576-5347    Fax: +82-2-572-6683    E-mail: katrdsubmit@lungkorea.org                

Copyright © 2024 by The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Developed in M2PI

Close layer
prev next