Interleukin-13 induces mucin 5AC production involving STAT6/SPDEF in human airway epithelial cells

Cell Commun Adhes. 2010 Aug;17(4-6):83-92. doi: 10.3109/15419061.2010.551682. Epub 2011 Jan 28.


Mucus hypersecretion is commonly observed in many chronic airway inflammatory diseases. Mucin 5AC (MUC5AC) is a major airway mucin because of its high expression in goblet cells. Here, the authors identified a gene called SAM domain-containing prostate-derived Ets factor (SPDEF) that was induced by interleukin (IL)-13. Their results showed that specific knockdown of SPDEF reduced IL-13-induced MUC5AC expression in human airway epithelial cells. This finding was associated with decreased expression of anterior gradient 2 (AGR2) and Ca(2+)-activated Cl(-) channel (CLCA1), which regulate IL-13-mediated MUC5AC overproduction. Furthermore, transfection with SPDEF siRNA enhanced expression of forkhead box a2 (Foxa2), a key transcription factor that is known to prevent mucus production. The authors also demonstrated that the repression of STAT6 inhibited expression of SPDEF and MUC5AC induced by IL-13. These results show that SPDEF plays a critical role in regulating a transcriptional network mediating IL-13-induced MUC5AC synthesis dependent on STAT6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cells, Cultured
  • Chloride Channels / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / metabolism
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Humans
  • Interleukin-13 / metabolism*
  • Mucin 5AC / biosynthesis*
  • Mucoproteins
  • Oncogene Proteins
  • Polymerase Chain Reaction
  • Proteins / genetics
  • Proto-Oncogene Proteins c-ets / genetics*
  • RNA, Small Interfering
  • Respiratory Mucosa / metabolism*
  • STAT6 Transcription Factor / genetics*


  • AGR2 protein, human
  • CLCA1 protein, human
  • Chloride Channels
  • FOXA2 protein, human
  • Interleukin-13
  • Mucin 5AC
  • Mucoproteins
  • Oncogene Proteins
  • Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Small Interfering
  • SPDEF protein, human
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Hepatocyte Nuclear Factor 3-beta