Biochemical and Biophysical Research Communications
Anti-fibrotic effects of theophylline on lung fibroblasts
Section snippets
Materials and methods
Materials. Human Transforming growth factor-β1(TGF-β1), theophylline, dibutyryl cAMP (a cAMP analog), Rp-cAMPS triethylammonium salt (a specific PKA inhibitor, Rp-cAMP), and water-soluble dexamethasone were purchased from Sigma (St. Louis, MO). Isogen was purchased from Nippon Gene (Tokyo, Japan). The Cell Counting Kit-8 was from Dojindo Laboratories (Kumamoto, Japan).
Cell culture. Normal human lung fibroblast (NHLF) (Sanko Jyunyaku, Tokyo, Japan) and human lung fibroblast cell line (WI-38)
Theophylline inhibits TGF-β-induced COL1 mRNA expression in NHLF and WI-38 cells
TGF-β, one of the potent inducers of COL1, is involved in the pathogenesis of airway fibrosis in both asthma and COPD [12]. To investigate the inhibitory effect of theophylline on TGF-β-induced COL1 mRNA expression in human lung fibroblasts, NHLF and WI-38 cells were treated with TGF-β in the presence or absence of theophylline. The amount of COL1 mRNA expression was determined by the real-time PCR method. Theophylline decreased TGF-β-induced COL1 mRNA expression in NHLF cells (Fig. 1A) and
Discussion
Theophylline, clinically used in the management of airway diseases over the past 50 years, has been demonstrated to exert not only a bronchodilating effect, but also other pleiotropic benefits, including anti-inflammatory effects, improvement of respiratory muscle function, and enhancement of mucociliary clearance [3]. So far, however, the direct effect of theophylline on airway fibrosis, one of the features of airway remodeling, has not been assessed. Our examination of whether theophylline
Acknowledgments
We thank Yoko Habe for secretarial assistance. This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
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