Anti-fibrotic effects of theophylline on lung fibroblasts.
Anti-fibrotic effects of theophylline on lung fibroblasts.
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DOI：
10.1016/j.bbrc.2006.01.018
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发表时间：
2006-03
影响因子：
3.1
通讯作者：
Y. Yano;Mitsuhiro Yoshida;S. Hoshino;Koji Inoue;H. Kida;M. Yanagita;T. Takimoto;H. Hirata;T. Kijima;T. Kumagai;T. Osaki;I. Tachibana;I. Kawase
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文献类型：
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作者：
Y. Yano;Mitsuhiro Yoshida;S. Hoshino;Koji Inoue;H. Kida;M. Yanagita;T. Takimoto;H. Hirata;T. Kijima;T. Kumagai;T. Osaki;I. Tachibana;I. Kawase
茶碱用于治疗哮喘和慢性阻塞性肺疾病已有50多年的历史。它不仅具有扩张支气管的作用，而且还具有抗炎作用，有利于抑制包括上皮下纤维化在内的呼吸道重塑。然而，到目前为止，茶碱是否对呼吸道纤维化有直接的抑制作用还没有确定。为了阐明这个问题，我们研究了茶碱是否影响肺成纤维细胞的功能。茶碱抑制转化生长因子-β诱导的肺成纤维细胞I型胶原(COL1mRNA)的表达，抑制胎牛血清和转化生长因子-β诱导的α-SMA蛋白诱导的成纤维细胞增殖。CAMP类似物也抑制转化生长因子-β诱导的肺成纤维细胞COL1mRNA的表达。蛋白激酶A抑制剂可减弱茶碱对转化生长因子-β诱导的COL1mRNA表达的抑制作用。这些结果表明，茶碱至少部分地通过cAMP-PKA途径发挥抗纤维化作用。
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-β-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited fibroblast proliferation stimulated by FBS and TGF-β-induced α-SMA protein. A cAMP analog also inhibited TGF-β-induced COL1 mRNA expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of theophylline on TGF-β-induced COL1 mRNA expression. These results indicate that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP-PKA pathway.