Nakamura Y, Tate L, Ertl R F, Kawamoto M, Mio T, Adachi Y, Romberger D J, Koizumi S, Gossman G, Robbins R A
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Am J Physiol. 1995 Sep;269(3 Pt 1):L377-87. doi: 10.1152/ajplung.1995.269.3.L377.
Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.
慢性支气管炎常导致不可逆的气道阻塞。气道结构改变伴气道结缔组织异常被认为在此过程中起重要作用。我们推测，气道内衬的上皮细胞通过引导成纤维细胞增殖来调节支气管周围纤维化和固定性气道阻塞的发展。为评估这一点，我们检测了牛支气管上皮细胞条件培养基对人肺成纤维细胞增殖的刺激活性。该条件培养基在无血清培养系统中以浓度依赖方式刺激成纤维细胞增殖。成纤维细胞生长刺激活性具有异质性，分子量大于50 kDa和约10 kDa。支气管上皮细胞条件培养基还含有成纤维细胞生长抑制因子，包括转化生长因子（TGF）-β以及基于吲哚美辛敏感性的环氧化酶产物。TGF-β似乎促成了条件培养基诱导的成纤维细胞形态变化。人肺成纤维细胞与支气管上皮细胞共培养导致成纤维细胞增殖受到刺激。总之，气道上皮细胞似乎调节成纤维细胞增殖，并可能在慢性支气管炎的支气管周围纤维化中起作用。
