Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Inflammation. 2009 Dec;32(6):387-92. doi: 10.1007/s10753-009-9147-x.
Fibroblasts are important cells that are involved in modulation of fibrosis after injuries. In some uncontrollable inflammatory processes, excess fibroblasts migrate around the small airway. The pathogenesis of chronic obstructive pulmonary disease is related to fibrosis around the small airways. The aim of the current study was to investigate the effect of procaterol, a second-generation beta (2)-agonist, on migration of human fetal lung fibroblasts (HFL-1) induced by human plasma fibronectin (HFn). Using the blindwell chamber technique, 10(-8) M procaterol inhibited migration of HFL-1 (control, 100%; 10(-8) M, 73.2 +/- 4.9%; n = 6, p < 0.05). The inhibitory effect of procaterol was concentration-dependent. Although a beta 2-receptor inhibitor, ICI 181551, blocked the inhibitory effect of procaterol, a beta 1-receptor inhibitor, atenolol, did not. Because a cyclic AMP-dependent protein kinase (PKA) inhibitor, KT5720, blocked the effect of procaterol, the cyclic AMP-PKA pathway may be involved in the migration inhibitory process. Procaterol, which is prescribed mainly for treatment of bronchial asthma, might be a useful drug for inhibiting lung fibrosis following injuries to the lung.
成纤维细胞是一种重要的细胞，参与损伤后的纤维化调节。在一些不可控的炎症过程中，过多的成纤维细胞会迁移到小气道周围。慢性阻塞性肺疾病的发病机制与小气道周围的纤维化有关。本研究的目的是探讨第二代β2-激动剂（procaterol）对人血浆纤维连接蛋白（HFn）诱导的人胎肺成纤维细胞（HFL-1）迁移的影响。采用盲孔室技术，10-8 M procaterol 抑制 HFL-1 的迁移（对照组 100%；10-8 M，73.2±4.9%；n=6，p<0.05）。Procaterol 的抑制作用呈浓度依赖性。虽然β2-受体抑制剂 ICI 181551 阻断了 procaterol 的抑制作用，但β1-受体抑制剂 atenolol 则没有。由于环磷酸腺苷依赖性蛋白激酶（PKA）抑制剂 KT5720 阻断了 procaterol 的作用，环磷酸腺苷-PKA 途径可能参与了迁移抑制过程。Procaterol 主要用于治疗支气管哮喘，可能是一种抑制肺损伤后肺纤维化的有用药物。
