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RESEARCH PRODUCT

The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma

Angela Marina MontalbanoS. La GruttaAnna BonannoRosalia GagliardoPascal ChanezGiulia AnzaloneC Di SanoLoredana RiccobonoMirella ProfitaDelphine GrasGiusy Daniela AlbanoMark Gjomarkaj

subject

MaleNeutrophilsSmad2 ProteinSMADEosinophilAdrenal Cortex HormoneSeverity of Illness IndexAdrenal Cortex HormonesImmunology and AllergyAge FactorPhosphorylationChildLungNeutrophilAge FactorsBronchodilator Agentsmedicine.anatomical_structureFemalemedicine.symptomCase-Control StudieHumanSignal TransductionGranulocyte activationAdolescentImmunologyAge Factors; Humans; Child; Macrophage-1 Antigen; Adrenal Cortex Hormones; Granulocytes; Neutrophils; Phosphorylation; Eosinophils; Adolescent; Signal Transduction; Male; Severity of Illness Index; Respiratory Mucosa; Asthma; Transforming Growth Factor beta1; Epithelial Cells; Lung; Smad2 Protein; Case-Control Studies; Smad7 Protein; Sputum; Administration Inhalation; Bronchodilator Agents; Cell Line; Female; Cell AdhesionMacrophage-1 AntigenCD18InflammationRespiratory MucosaGranulocyteCell LineSmad7 ProteinTransforming Growth Factor beta1Administration InhalationCell AdhesionmedicineHumansCell adhesionBronchodilator AgentPharmacologyEpithelial Cellbusiness.industrySputumGranulocyteEpithelial CellsEosinophilAsthmaEosinophilsCase-Control StudiesImmunologySputumbusinessGranulocytes

description

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.

yearjournalcountryeditionlanguage
2013-07-01International Journal of Immunopathology and Pharmacology
https://doi.org/10.1177/039463201302600316