Anti-fibrotic effects of theophylline on lung fibroblasts.
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.
Yano
Yukihiro
Y
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Yoshida
Mitsuhiro
M
Hoshino
Shigenori
S
Inoue
Koji
K
Kida
Hiroshi
H
Yanagita
Masahiko
M
Takimoto
Takayuki
T
Hirata
Haruhiko
H
Kijima
Takashi
T
Kumagai
Toru
T
Osaki
Tadashi
T
Tachibana
Isao
I
Kawase
Ichiro
I
D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013806:Theophylline / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D024042:Collagen Type I; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D013806:Theophylline; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases