The role of transforming growth factor-β1 in airway inflammation of childhood asthma

Int J Immunopathol Pharmacol. 2013 Jul-Sep;26(3):725-38. doi: 10.1177/039463201302600316.

Abstract

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Age Factors
  • Asthma / diagnosis
  • Asthma / drug therapy
  • Asthma / immunology
  • Asthma / metabolism*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage
  • Case-Control Studies
  • Cell Adhesion
  • Cell Line
  • Child
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Humans
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism*
  • Lung / physiopathology
  • Macrophage-1 Antigen / metabolism
  • Male
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phosphorylation
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Severity of Illness Index
  • Signal Transduction* / drug effects
  • Smad2 Protein / metabolism
  • Smad7 Protein / metabolism
  • Sputum / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Macrophage-1 Antigen
  • SMAD2 protein, human
  • SMAD7 protein, human
  • Smad2 Protein
  • Smad7 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1