The role of transforming growth factor-β1 in airway inflammation of childhood asthma.
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.
Institute of Biomedicine and Molecular Immunology, Unit of Immunopathology and Pharmacology of the Respiratory System, A. Maurizio Vignola Laboratories, Italian National Research Council, Palermo, Italy.
R
R
Gagliardo
P
P
Chanez
M
M
Gjomarkaj
S
S
La Grutta
A
A
Bonanno
A M
AM
Montalbano
C
C
Di Sano
G D
GD
Albano
D
D
Gras
G
G
Anzalone
L
L
Riccobono
M
M
Profita
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000367:Age Factors; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D002448:Cell Adhesion; D002460:Cell Line; D002648:Child; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D013183:Sputum / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D016177:Macrophage-1 Antigen; C497782:SMAD2 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051906:Smad7 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1