Tiotropium sustains the anti-inflammatory action of olodaterol via the cyclic AMP pathway

Costa, L. and Roth, M. and Miglino, N. and Keglowich, L. and Zhong, J. and Lardinois, D. and Tamm, M. and Borger, P.. (2014) Tiotropium sustains the anti-inflammatory action of olodaterol via the cyclic AMP pathway. Pulmonary pharmacology & therapeutics, Vol. 27, H. 1. pp. 29-37.

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Official URL: http://edoc.unibas.ch/dok/A6338068

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Mesenchymal cells (fibroblasts) of the airway wall respond to cholinergic stimulation by releasing pro-inflammatory and chemotactic cytokines and may thus contribute to chronic inflammation of the lung. Here, we studied the anti-inflammatory potential of olodaterol, a long acting beta2-adrenergic receptor agonist, and tiotropium, a long-acting muscarinic receptor antagonist, and whether they interact at the level of the cyclic AMP dependent signaling pathway. Pulmonary fibroblasts of asthmatic (n = 9) and non-asthmatic (n = 8) subjects were stimulated with the muscarinic receptor agonist carbachol and interleukin-1beta (IL-1 beta) in presence or absence of tiotropium or olodaterol alone, or their combination. We also measured cAMP levels and phosphorylation of the cAMP response element binding protein (CREB). As single components, carbachol, olodaterol and tiotropium did not affect IL-6 and IL-8 release. Carbachol concentration-dependently enhanced the production of IL-1beta-induced IL-6 and IL-8, which was blocked by the simultaneous addition of tiotropium. The combination of olodaterol plus tiotropium further reduced IL-6 and IL-8 release. Olodaterol induced cAMP and the phosphorylation of CREB, an effect counteracted by carbachol, but rescued by tiotropium. We conclude that olodaterol plus tiotropium cooperate to decrease the inflammatory response in pulmonary fibroblasts in vitro.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Tamm, Michael and Roth-Chiarello, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:06 Feb 2015 09:59

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