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

Abstract

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.

• Authors: Charles L Hardy, Jeanne S Lemasurier, Fredrik Olsson, Thanh Dang, Jun Yao, Ming Yang, Magdalena Plebanski, David J Phillips, Richard Mollard, Jennifer M Rolland, Robyn E O'Hehir
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 42 Issue 6 Pg. 667-75 (Jun 2010) ISSN: 1535-4989 [Electronic] United States
• PMID: 19635933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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