β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD

6533b832fe1ef96bd129ad06

RESEARCH PRODUCT

β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD

Giusy Daniela Albano Giusy Daniela Albano Anna Bonanno Michael P. Pieper Paola Casarosa Angela Marina Montalbano Maria Ferraro Mirella Profita Liboria Siena Loredana Riccobono Mark Gjomarkaj

subject

Agonist medicine.medical_specialty medicine.drug_class chemistry.chemical_compound Internal medicine TGF-β1 Anticholinergic drug Muscarinic acetylcholine receptor medicine COPD Receptor Molecular Biology Beta2 long acting COPD Chemistry Olodaterol Tiotropium bromide medicine.disease respiratory tract diseases Endocrinology Molecular Medicine Neutrophilic inflammation Bronchoconstriction medicine.symptom Acetylcholine medicine.drug

description

AbstractWe quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β2-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and TGF-β1 in HS is higher than in HC; 2) ISSs from COPD and HS caused increased neutrophil adhesion to 16-HBE when compared to ISSs from HC. The effect of ISSs from COPD was significantly reduced by TGF-β1 depletion or by the pretreatment with Olodaterol or Tiotropium alone or in combination, while the effect of ISSs from HS was significantly reduced by the pretreatment with Olodaterol alone; 3) mAChR2, mAChR3 and ChAT expression was increased in 16-HBE stimulated with ISSs from COPD and TGF-β1 depletion significantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-β1 increased mAChR2, mAChR3 and ChAT expression in 16-HBE; 5) Olodaterol did not affect the expression of mAChRs and ChAT in 16-HBE. Our findings support the use of β2 long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-β1-mediated neutrophilic inflammation in COPD.

year	journal	country	edition	language
2012-07-01	Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

10.1016/j.bbadis.2012.03.002 http://dx.doi.org/10.1016/j.bbadis.2012.03.002