IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic Mucous cells

Sci Rep. 2018 Jan 11;8(1):436. doi: 10.1038/s41598-017-18884-9.


Exposure to lipopolysaccharides (LPS) causes extensive neutrophilic inflammation in the airways followed by mucous cell hyperplasia (MCH) that is sustained by the anti-apoptotic protein, Bcl-2. To identify inflammatory factor(s) that are responsible for Bcl-2 expression, we established an organ culture system consisting of airway epithelial tissue from the rat nasal midseptum. The highest Muc5AC and Bcl-2 expression was observed when organ cultures were treated with brochoalveolar lavage (BAL) fluid harvested from rats 10 h post LPS instillation. Further, because BAL harvested from rats depleted of polymorphonuclear cells compared to controls showed increased Bcl-2 expression, analyses of cytokine levels in lavages identified IL-13 as an inducer of Bcl-2 expression. Ectopic IL-13 treatment of differentiated airway epithelial cells increased Bcl-2 and MUC5AC expression in the basal and apical regions of the cells, respectively. When Bcl-2 was blocked using shRNA or a small molecule inhibitor, ABT-263, mucous cell numbers were reduced due to increased apoptosis that disrupted the interaction of Bcl-2 with the pro-apoptotic protein, Bik. Furthermore, intranasal instillation of ABT-263 reduced the LPS-induced MCH in bik +/+ but not bik -/- mice, suggesting that Bik mediated apoptosis in hyperplastic mucous cells. Therefore, blocking Bcl-2 function could be useful in reducing IL-13 induced mucous hypersecretion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Bronchoalveolar Lavage Fluid / immunology
  • Hyperplasia
  • Inflammation / metabolism*
  • Interleukin-13 / metabolism*
  • Lipopolysaccharides / adverse effects*
  • Male
  • Mucin 5AC / metabolism
  • Nasal Septum / cytology*
  • Nasal Septum / metabolism
  • Nasal Septum / pathology
  • Organ Culture Techniques
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats


  • Interleukin-13
  • Lipopolysaccharides
  • Muc5ac protein, rat
  • Mucin 5AC
  • Proto-Oncogene Proteins c-bcl-2