title: IL-13-induced MUC5AC production and goblet cell differentiation is steroid resistant in human airway cells.
abstract: BACKGROUND
  Glucocorticosteroids (GCS) are used to treat bronchial asthma, but are not uniformly effective, especially in severe asthma. IL-13 is a T helper type 2 cytokine implicated in the pathogenesis of asthma, and IL-13 induces mucus production and goblet cell hyperplasia in airway epithelial cells. The effect of GCS on IL-13-induced mucin production is not well characterized.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effect of dexamethasone (Dex), a potent synthetic GCS, on IL-13-induced MUC5AC mucin expression and goblet cell proliferation in differentiated normal human bronchial epithelial cells (NHBECs).
  
  
  METHODS
  NHBECs were cultured for 14 days at an air-liquid interface with IL-13, with or without Dex. MUC5AC protein secretion and mRNA expression was determined using ELISA and quantitative real-time PCR. IL-8 production was assayed using ELISA. Histochemical analysis was performed using H&E and periodic acid-Schiff stain, and MUC5AC immunostaining.
  
  
  RESULTS
  Although Dex dose dependently inhibited IL-8 release induced by 5 ng/mL IL-13, Dex 0.001-1 μg/mL had no effect on IL-13 induced MUC5AC protein secretion or mRNA expression. Dex paradoxically increased MUC5AC induced by IL-13 at 0.5 and 1 ng/mL, but had no effect alone or with IL-13 at 0.1 ng/mL. Dex 0.001-1 μg/mL did not inhibit the differentiation of cells into goblet cells and MUC5AC-positive cells induced by IL-13.
  
  
  CONCLUSIONS
  Dex at therapeutic concentrations did not inhibit the effects of IL-13 on goblet cell differentiation, characteristic of severe asthma. Paradoxically, MUC5AC production was increased with lower dose IL-13 exposure. This may lead to airway mucus obstruction commonly seen in life-threatening asthma.
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kanoh
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: B K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020397:Goblet Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis; D055271:Mucin 5AC / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018793:Interleukin-13; D016209:Interleukin-8; D055271:Mucin 5AC; D012333:RNA, Messenger; D003907:Dexamethasone