title: Glucocorticoids inhibit MUC5AC production induced by transforming growth factor-α in human respiratory cells.
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.
authors: Department of Pediatrics, Gunma University Graduate School of Medicine, 3−39−15 Showa-machi, Maebashi, Gunma, Japan.
authors: Satoru
authors: S
authors: Takami
authors: Takahisa
authors: T
authors: Mizuno
authors: Takato
authors: T
authors: Oyanagi
authors: Hiromi
authors: H
authors: Tadaki
authors: Tomoko
authors: T
authors: Suzuki
authors: Kazuhiro
authors: K
authors: Muramatsu
authors: Takumi
authors: T
authors: Takizawa
authors: Hirokazu
authors: H
authors: Arakawa
mesh_terms: D001249:Asthma / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D055271:Mucin 5AC / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D055271:Mucin 5AC; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases