尾₂ long-acting and anticholinergic drugs control TGF-尾1-mediated neutrophilic inflammation in COPD

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• 作者：Mirella Profita^a ; ^{profita@ibim.cnr.it} ; Anna Bonanno^a ; Angela Marina Montalbano^a ; Giusy Daniela Albano^a ; ^b ; Loredana Riccobono^a ; Liboria Siena^a ; Maria Ferraro^a ; Paola Casarosa^c ; Michael Paul Pieper^c ; Mark Gjomarkaj^a
• 关键词：TGF-尾1 ; COPD ; Neutrophilic inflammation ; Beta2 long acting ; Anticholinergic drug
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 期刊代码：19_09254439
• 类别：bio
• 出版时间：July, 2012
• 卷：1822
• 期：7
• 页码：1079-1089
• 文件大小：1110 K

摘要

We quantified TGF-尾1 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-尾1 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 尾₂-adrenoceptor agonist) and Tiotropium Spiriva庐, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-尾1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and TGF-尾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 significantly reduced by TGF-尾1 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-尾1 depletion significantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-尾1 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 尾₂ long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-尾1-mediated neutrophilic inflammation in COPD.