Beta2 long-acting and anticholinergic drugs control TGF-beta1-mediated neutrophilic inflammation in COPD

We quanti fi ed TGF-beta1 and acetylcholine (ACh) concentratio ns 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-beta1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experi-ments in human bronchial epithelial cells (16-HBE ). Finally, we evaluated the effect s of Olodaterol (a novel inhaled beta2-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-beta1 and ACh concen-trations are increased in ISSs from COPD in comparison to HC and HS, and TGF- ?1 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 signi fi cantly reduced by TGF-beta1 depletion or by the pretreatment with Olo-daterol or Tiotropium alone or in combination, while the effect of ISSs from HS was signi ficantly reduced by the pretr eatment with Olodaterol alone; 3) mAChR2, mAChR3 and ChAT expressio n was increased in 16-HBE stimulated with ISSs from COPD and TGF-beta1 deple tion signi fi cantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-beta1 increased mAChR2, mAChR3 and ChAT expression in 16-HBE; 5) Olodaterol did not affect the expression of mAChRs and ChAT in 16-HBE. Our fi ndings support the use of beta2 long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-beta1-mediated neutrophilic in flammation in COPD.