Pentoxifylline and its active metabolite lisofylline attenuate transforming growth factor β1-induced asthmatic bronchial fibroblast-to-myofibroblast transition

Abstract

Bronchial asthma is characterized by persistent airway inflammation and airway wall remodeling. Among many different cells and growth factors triggering changes in bronchi structure, transforming growth factor β₁-induced fibroblast to myofibroblast transition is believed to be very important. The aim of this study was to evaluate whether theophylline (used in asthma therapy) and two other methylxanthines (pentoxifylline and its active metabolite lisofylline), may affect transforming growth factor β₁-induced fibroblast to myofibroblast transition in bronchial fibroblasts derived from asthmatic patients. We show here for the first time that selected methylxanthines effectively reduce transforming growth factor β₁-induced myofibroblast formation in asthmatic bronchial fibroblast populations. PTX was found to be the most effective methylxanthine. The number of differentiated myofibroblasts after PTX, LSF and THEO administration was reduced at least twofold. Studies on the use of methylxanthines opens a new perspective in the development of novel strategies in asthma therapy through their two-pronged, anti-inflammatory and anti-fibrotic action. In the future they can be considered as promising anti-fibrotic drugs.