Anti-fibrotic effects of theophylline on lung fibroblasts |
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Authors: | Yano Yukihiro Yoshida Mitsuhiro Hoshino Shigenori Inoue Koji Kida Hiroshi Yanagita Masahiko Takimoto Takayuki Hirata Haruhiko Kijima Takashi Kumagai Toru Osaki Tadashi Tachibana Isao Kawase Ichiro |
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Affiliation: | Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. |
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Abstract: | Theophylline has been used in the management of bronchial asthma and chronic obstructive pulmonary disease for over 50 years. It has not only a bronchodilating effect, but also an anti-inflammatory one conducive to the inhibition of airway remodeling, including subepithelial fibrosis. To date however, whether theophylline has a direct inhibitory effect on airway fibrosis has not been established. To clarify this question, we examined whether theophylline affected the function of lung fibroblasts. Theophylline suppressed TGF-beta-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited fibroblast proliferation stimulated by FBS and TGF-beta-induced alpha-SMA protein. A cAMP analog also inhibited TGF-beta-induced COL1 mRNA expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of theophylline on TGF-beta-induced COL1 mRNA expression. These results indicate that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP-PKA pathway. |
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Keywords: | Theophylline Airway remodeling Asthma COPD TGF-β Collagen cAMP PKA Fibroblast |
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