In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD
| Autor: | Angela Marina Montalbano, Maria Ferraro, Mirella Profita, Stefania Gerbino, Giusy Daniela Albano, Loredana Riccobono, Mark Gjomarkaj, Anna Bonanno, Paola Casarosa, Michael P. Pieper |
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| Přispěvatelé: | Profita, M, Riccobono, L, Montalbano, AM, Bonanno, A, Ferraro, M, Albano, GD, Gerbino, S, Casarosa, P, Pieper, MP, Gjomarkaj, M |
| Rok vydání: | 2012 |
| Předmět: |
Male
Immunology Scopolamine Derivatives Apoptosis CD8-Positive T-Lymphocytes Pharmacology Systemic inflammation Cholinergic Antagonists Choline Choline O-Acetyltransferase Pulmonary Disease Chronic Obstructive Annexin Muscarinic acetylcholine receptor medicine Humans Immunology and Allergy Lymphocyte Count Tiotropium Bromide Caspase Aged Receptor Muscarinic M3 Caspase 8 COPD biology Caspase 3 Systemic inflammation Non-neuronal components of cholinergic system Caspases NF B pathway business.industry NF-kappa B Hematology Tiotropium bromide Middle Aged medicine.disease respiratory tract diseases Enzyme Activation biology.protein Female medicine.symptom business Acetylcholine Protein Binding Signal Transduction medicine.drug |
| Zdroj: | Immunobiology. 217:345-353 |
| ISSN: | 0171-2985 |
| DOI: | 10.1016/j.imbio.2011.07.013 |
| Popis: | Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspases 3 and 8 activity and choline levels, in PBT-cells from COPD patients. We showed that: (1) apoptosis, mAChR M(3) and ChAT expression and the CD3+ and CD8+ ACh-binding are increased in PBT-cells from COPD patients when compared to C subjects, while CD4+/CD8+ ratio of ACh-binding to PBT cells was reduced in COPD; (2) choline levels are higher in serum and PBT-cells extracts from COPD patients than in S and C; (3) Tiotropium and HCh-3 reduced CD4+ and increased CD8+ apoptosis via caspases 3 and 8 activities and via IκB mediated mechanisms in COPD patients. This study suggests the involvement of non-neuronal components of cholinergic system in the regulation of PBT-cell apoptosis in COPD and demonstrates that Tiotropium regulates CD4+ and CD8+ PBT-cell apoptosis. It provides novel putative pharmacological targets for the resolution of systemic inflammation in COPD. |
| Databáze: | OpenAIRE |
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