ADRB2 and CHRM3 gene expression in blood leukocytes of patients with acute exacerbation of chronic obstructive pulmonary disease
https://doi.org/10.18093/0869-0189-2015-25-2-151-156
Abstract
This pilot study was aimed at evaluation of ADRB2 and CHRM3 gene expression in COPD. Methods. We evaluated ADRB2 and CHRM3 gene expression in blood leukocytes from 29 patients with acute exacerbation of COPD (GOLD stage II to III, Group D) before and after 2-week combined therapy including antimicrobials, tiotropium bromide, formoterol and an inhaled steroid. ADRB2- and CHRM3-specific mRNA content was determined in leukocytes using real-time PCR. Results. Mean gene expression levels did not differ before and after treatment. However, we found a significant correlation between changes in ADRB2 and CHRM3 gene expression, change in FEV1 and post-treatment C-reactive protein level.
Conclusion. The results confirm a possibility to affect adrenoceptors using beta agonists and inhaled steroids and to inhibit M-cholinoreceptor expression with M3-cholinolytics and inhaled steroids.
About the Authors
A. B. Chukhlovin
State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo ul., Saint-Petersburg, 197089, Russia
Russian Federation
Russian Federation
MD, Professor, Deputy Director, R.M.Gorbacheva Scientific and Research Institute of Pediatric Oncology, Haematology and Transplantology, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 233-48-51;
N. A. Kuzubova
State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo ul., Saint-Petersburg, 197089, Russia
Russian Federation
Russian Federation
MD, Professor, Deputy Director, Scientific and Research Pulmonology Institute, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 234-17-69;
N. D. Elshin
State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo ul., Saint-Petersburg, 197089, Russia
Russian Federation
Russian Federation
PhD student, Department of Clinical and Laboratory Diagnostics, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: / fax: (812) 233-97-26;
O. N. Titova
State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo ul., Saint-Petersburg, 197089, Russia
Russian Federation
Russian Federation
MD, Director, Scientific and Research Pulmonology Institute, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; tel.: (812) 499-68-40
References
1. Chuchalin A.G., Avdeev S.N., Aysanov Z.R. et al. Federal guidelines on diagnosis and management of chronic obstructive pulmonary disease. Moscow: Rossiyskoe respiratornoe obshchestvo; 2013 (in Russian).
2. Dale Ph.R., Cernecka H., Schmidt M. et al. The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease. Curr. Opin. Pharmacol. 2014; 16: 31–42.
3. Ogorodova L.M., Chernyak B.A., Kozina O.V. et al. Molecular aspects of different phenotypes of chronic obstructive pulmonary disease. Pul'monologiya. 2013; 1: 5–11 (in Russian).
4. Kin N.W., Sanders V.M. It takes nerve to tell T and B cells what to do. J. Leukoc. Biol. 2006; 79 (6): 1093–1104.
5. Yu X.Y., Lin S.G., Wang X.M. et al. Evidence for coexistence of three #b-adrenoceptor subtypes in human peripheral lymphocytes. Clin. Pharmacol. Ther. 2007; 81 (5): 654–658.
6. Fujii T., Takada-Takatori Y., Kawashima K. Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy. J. Pharmacol. Sci. 2008; 106 (2): 186–192.
7. Klement R.F., Lavrushin A.A., Ter-Pogosyan P.A. User guide on formulas and tables of reference values for general spirometric parameters. Leningrad; 1986 (in Russian).
8. Moniotte S., Vaerman J.L., Kockx M.M. et al. Real-time RT-PCR for the detection of beta-adrenoceptor messenger RNAs in small human endomyocardial biopsies. J. Mol. Cell. Cardiol. 2001; 33 (12): 2121–2133.
9. Patel N., Itakura T., Gonzalez J.M. Jr et al. GPR158, an orphan member of G protein-coupled receptor family C: glucocorticoid-stimulated expression and novel nuclear role. PLoS One. 2013; 8 (2): e57843. DOI: 10.1371/journal.pone.0057843.
10. Braden G.L., Germain M.J., Mulhern J.G. et al. Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients. Chest. 1998; 114 (2): 380–387.
11. Bjermer L., Bengtsson Th., Jorup C. et al. Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD. Respir. Med. 2013; 107 (1): 84–90.
12. Theron A.J., Steel H.C., Tintinger G.R. et al. Can the anti-inflammatory activities of #b2-agonists be harnessed in the clinical setting? Drug Des .Devel. Ther. 2013; 7: 1387–1398.
13. Black J.L., Oliver B.G.G., Roth M. Molecular mechanisms of combination therapy with inhaled corticosteroids and long-acting #b-agonists. Chest. 2009; 136 (4): 1095–1100.
14. Dalby Ch., Polanowski T., Larsson Th. et al. The bioavailability and airway clearance of the steroid component of budesonide / formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir. Res. 2009; 10: 104. DOI: 10.1186/1465-9921-10-104.
15. Rüdiger J.J., Gencay M., Yang J.Q. et al. Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma. Respirology. 2013; 18 (5): 840–847.
16. Barnes P.J. Scientific rationale for inhaled combination therapy with long-acting #b2-agonists and corticosteroids. Eur. Respir. J. 2002; 19 (1): 182–191.
17. Oakley R.H., Cidlowski J.A. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J. Allergy Clin. Immunol. 2013; 132 (5): 1033–1044.
18. Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Differential expression of the #b2-adrenoreceptor and M3-cholinoreceptor genes in bronchial mucosa of patients with asthma and chronic obstructive pulmonary disease. Ann. Allergy Asthma Immunol. 2012; 108 (1): 39–43.
19. Kerstjens H.A.M., Engel M., Dahl R. et al. Tiotropium in asthma poorly controlled with standard combination therapy. N. Engl. J. Med. 2012; 367 (13): 1198–1207.
20. Gosens R., Zaagsma J., Meurs H. et al. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res. 2006; 7: 73.
Review
For citations:
Chukhlovin A.B., Kuzubova N.A., Elshin N.D., Titova O.N. ADRB2 and CHRM3 gene expression in blood leukocytes of patients with acute exacerbation of chronic obstructive pulmonary disease. PULMONOLOGIYA. 2015;25(2):151-156. (In Russ.) https://doi.org/10.18093/0869-0189-2015-25-2-151-156
Views:
774
Email this article 