RT Journal Article
SR Electronic
T1 Cigarette smoke augments MUC5AC mucin production via TLR3-EGFR pathway in airway epithelial cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3889
VO 42
IS Suppl 57
A1 Kuninobu Kanai
A1 Akira Koarai
A1 Hisatoshi Sugiura
A1 Tomohiro Ichikawa
A1 Takashi Kikuchi
A1 Keiichiro Akamatsu
A1 Tsunahiko Hirano
A1 Masanori Nakanishi
A1 Kazuto Matsunaga
A1 Yoshiaki Minakata
A1 Masakazu Ichinose
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P3889.abstract
AB Virus infections are a major cause of COPD exacerbations. Recently, toll-like receptor 3 (TLR3) has been shown to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether cigarette smoke, which is involved in the pathogenesis of COPD, enhances the mucin production via TLR3-epidermal growth factor receptor (EGFR) pathway in airway epithelial cells. The effect of cigarette smoke extract (CSE) on the production of a major airway mucin, MUC5AC, in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. CSE significantly potentiated the production of MUC5AC mucin in the epithelial cells after stimulation with poly(I:C) and the potentiation was inhibited by treatment with N-acetylcysteine, an antioxidant. CSE potentiated EGFR ligands (TGF-α and amphiregulin) production in the poly(I:C)-treated cells, and the CSE-augmented MUC5AC mucin production was inhibited by the neutralizing antibodies of EGFR or EGFR ligands. In addition, the augmented MUC5AC mucin production was inhibited by EGFR inhibitors (AG1378 and BIBX1382) or ERK inhibitor (U0126). These data suggest that cigarette smoke augments TLR3-stimulated mucin production in airway epithelial cells via EGFR and ERK signaling. Modulation of this pathway may be a therapeutic target for viral-induced mucin overproduction in exacerbations of COPD.