Interleukin-13 regulates secretion of the tumor growth factor-{beta} superfamily cytokine activin A in allergic airway inflammation

Am J Respir Cell Mol Biol. 2010 Jun;42(6):667-75. doi: 10.1165/rcmb.2008-0429OC. Epub 2009 Jul 27.


Activin A is a member of the TGF-beta superfamily and plays a role in allergic inflammation and asthma pathogenesis. Recent evidence suggests that activin A regulates proinflammatory cytokine production and is regulated by inflammatory mediators. In a murine model of acute allergic airway inflammation, we observed previously that increased activin A concentrations in bronchoalveolar lavage (BAL) fluid coincide with Th2 cytokine production in lung-draining lymph nodes and pronounced mucus metaplasia in bronchial epithelium. We therefore hypothesized that IL-13, the key cytokine for mucus production, regulates activin A secretion into BAL fluid in experimental asthma. IL-13 increased BAL fluid activin A concentrations in naive mice and dose dependently induced activin A secretion from cultured human airway epithelium. A key role for IL-13 in the secretion of activin A into the BAL fluid during allergic airway inflammation was confirmed in IL-13-deficient mice. Eosinophils were not involved in this response because there was no difference in BAL fluid activin A concentrations between wild-type and eosinophil-deficient mice. Our data highlight an important role for IL-13 in the regulation of activin A intraepithelially and in BAL fluid in naive mice and during allergic airway inflammation. Given the immunomodulatory and fibrogenic effects of activin A, our findings suggest an important role for IL-13 regulation of activin A in asthma pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors / metabolism
  • Activins / metabolism*
  • Animals
  • Asthma / immunology
  • Asthma / metabolism*
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Inhibin-beta Subunits / metabolism
  • Interleukin-13 / administration & dosage
  • Interleukin-13 / deficiency
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism*
  • Interleukin-5 / deficiency
  • Interleukin-5 / genetics
  • Metaplasia
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Ovalbumin
  • Pneumonia / immunology
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / metabolism
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Signal Transduction
  • Time Factors
  • Transforming Growth Factor beta / metabolism*


  • Interleukin-13
  • Interleukin-5
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • activin A
  • inhibin beta A subunit
  • Activins
  • Ovalbumin
  • Inhibin-beta Subunits
  • Activin Receptors