Drug Design, Development and Therapy (Jan 2017)
Theophylline action on primary human bronchial epithelial cells under proinflammatory stimuli and steroidal drugs: a therapeutic rationale approach
Abstract
Luca Gallelli,1,* Daniela Falcone,1,* Roberto Cannataro,2 Mariarita Perri,2 Raffaele Serra,3 Girolamo Pelaia,3 Rosario Maselli,3 Rocco Savino,1 Giuseppe Spaziano,4 Bruno D’Agostino4 1Department of Health Science, University of Catanzaro, Catanzaro, 2Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, 3Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, 4Department of Experimental Medicine, School of Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy *These authors contributed equally to this work Abstract: Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli. Theophylline administrated alone was not able to reduce growth-stimulating signaling via extracellular signal-regulated kinases activation and matrix metalloproteases release, whereas it strongly counteracts this biochemical behavior when administered in the presence of corticosteroids. These data provide scientific evidence for supporting the rationale for the pharmacological use of theophylline and corticosteroid combined drug. Keywords: human bronchial epithelial cells, theophylline, corticosteroids, signal transduction
