Format

Send to

Choose Destination
Allergol Int. 2012 Sep;61(3):451-9. doi: 10.2332/allergolint.11-OA-0411. Epub 2012 Jul 25.

Glucocorticoids inhibit MUC5AC production induced by transforming growth factor-α in human respiratory cells.

Author information

1
Department of Pediatrics, Gunma University Graduate School of Medicine, 3−39−15 Showa-machi, Maebashi, Gunma, Japan.

Abstract

BACKGROUND:

Mucus hypersecretion from airway epithelium is a characteristic feature of severe asthma. Glucocorticoids (GCs) may suppress mucus production and diminish the harmful airway obstruction. We investigated the ability of GCs to suppress mRNA expression and protein synthesis of a gene encoding mucin, MUC5AC, induced by transforming growth factor (TGF)-α in human mucoepidermoid carcinoma (NCI-H292) cells and the molecular mechanisms underlying the suppression.

METHODS:

We determined if GCs such as dexamethasone (DEX), budesonide (BUD), and fluticasone (FP) could suppress MUC5AC production induced by a combination of TGF-α and double-strand RNA, polyinosinic-polycytidylic acid (polyI:C). MUC5AC mRNA expression and MUC5AC protein production were evaluated. The signaling pathways activated by TGF-α and their inhibition by GCs were tested using a phosphoprotein assay and MUC5AC promoter assay.

RESULTS:

DEX significantly suppressed the expression of MUC5AC mRNA and MUC5AC protein induced by TGF-α. The activation of the MUC5AC promoter by TGF-α was significantly inhibited by DEX. DEX did not affect activation of downstream pathways of the EGF receptor or mRNA stability of MUC5AC transcripts. DEX, BUD, and FP suppressed MUC5AC protein expression induced by a combination of TGF-α and polyI:C in a dose-dependent manner.

CONCLUSIONS:

GCs inhibited MUC5AC production induced by TGF-α alone or a combination of TGF-α and polyI:C; the repression may be mediated at the transcriptional but not post-transcriptional level.

PMID:
22824974
DOI:
10.2332/allergolint.11-OA-0411
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center