title: 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.
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; and Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wójcik-Pszczoła
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Hińcza
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Wnuk
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Kądziołka
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Koczurkiewicz
authors.affiliation: Department of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Michalik
mesh_terms: D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058628:Myofibroblasts / Q000502:physiology*; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D018927:Anti-Asthmatic Agents; D053773:Transforming Growth Factor beta1; C025189:lisofylline; D010431:Pentoxifylline