Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction
Cigarette smoke extract inhibits fibroblast-mediated collagen gel contraction
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DOI：
10.1152/ajplung.1998.274.4.l591
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发表时间：
1998-04-01
影响因子：
4.9
通讯作者：
Rennard, SI
中科院分区：
文献类型：
--
作者：
Carnevali, S;Nakamura, Y;Rennard, SI
吸烟是肺气肿的主要原因，其特征是肺泡壁被破坏。由于组织破坏代表了损伤和修复之间的平衡，我们假设香烟烟雾暴露可能通过抑制修复过程中的组织收缩而促进肺气肿的发展。为了部分评估这一假设，我们研究了香烟烟雾提取物(CSE)对体外培养的成纤维细胞介导胶原凝胶收缩能力的影响：CSE以浓度依赖的方式抑制成纤维细胞介导的凝胶收缩(P<；0.01)。CSE对已知的成纤维细胞收缩抑制剂前列腺素E-2的产生没有影响，细胞表面整合素的表达也没有变化。相反，纤维连接蛋白的产生受到抑制(P<；0.01)，外源性纤维连接蛋白的加入部分恢复了纤维连接蛋白的收缩活性，因此至少有一个机制可以解释CSE抑制凝胶收缩的机制。当CSE去除挥发性成分时，它对成纤维细胞介导的凝胶收缩的抑制活性较小。因此，我们还研究了香烟烟雾中的两种挥发性成分--丙烯醛和乙醛的影响。5 mU丙烯醛和0.5 mM乙醛对收缩有抑制作用。总而言之，香烟烟雾抑制了成纤维细胞介导的凝胶收缩，这种抑制至少部分是由于香烟烟雾的挥发性成分，并可能至少部分通过减少成纤维细胞纤维连接蛋白的产生而起作用。通过抑制修复，这些烟雾成分可能有助于肺气肿的发展。
Cigarette smoking, the major cause of pulmonary emphysema, is characterized by destruction of alveolar walls. Because tissue destruction represents a balance between injury and repair, we hypothesized that cigarette smoke exposure may contribute to the development of emphysema through the inhibition of tissue contraction during the repair process. To partially evaluate this hypothesis, we investigated the effects of cigarette smoke extract (CSE) on the ability of cultured fibroblasts to mediate collagen gel contraction in vitro: CSE inhibited fibroblast-mediated gel contraction in a concentration-dependent manner (P < 0.01). Production of prostaglandin E-2, a known inhibitor of fibroblast contraction, was unchanged by CSE as was cell surface integrin expression. In contrast, fibronectin production by fibroblasts was inhibited (P < 0.01), and addition of exogenous fibronectin partially restored the contractile activity, thus suggesting at least one mechanism to explain inhibition of gel contraction by CSE. When CSE was treated to remove volatile components, it showed less inhibitory activity on fibroblast-mediated gel contraction. Therefore, we also examined the effects of acrolein and acetaldehyde, two volatile components of cigarette smoke. Inhibition of contraction was observed at 5 mu M acrolein and at 0.5 mM acetaldehyde. In conclusion, cigarette smoke inhibited fibroblast-mediated gel contraction, and this inhibition was due, at least in part, to the volatile components of cigarette smoke and may be mediated, at least in part, by a decrease in fibroblast fibronectin production. By inhibition of repair, these smoke components may contribute to the development of pulmonary emphysema.