Hostettler K E, Roth M, Burgess J K, Gencay M M, Gambazzi F, Black J L, Tamm M, Borger P
Pulmonary Cell Research, Department of Research, University Hospital Basel, Basel, Switzerland.
Clin Exp Allergy. 2008 Aug;38(8):1309-17. doi: 10.1111/j.1365-2222.2008.03017.x. Epub 2008 May 22.
In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately.
The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model.
Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2+/-6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 microm indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-beta, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-beta antibodies.
These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-beta, which induces the prostaglandin E(2) synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication.
在健康肺组织中，气道上皮细胞（AEC）通过释放可溶性因子（如前列腺素和蛋白质）来调节成纤维细胞的增殖。纤维增殖性疾病和气道重塑可能是由于AEC产生的抑制因子不足，或成纤维细胞无法对其做出适当反应所致。
本研究旨在通过交互式细胞培养模型，研究原代人AEC对从健康和纤维化肺组织中获取的成纤维细胞增殖的影响。
16个AEC系中的14个的条件培养基（CM）显著抑制正常人肺成纤维细胞的增殖，抑制率为51.2±6.0%。AEC的CM对肺纤维化患者来源的成纤维细胞的增殖也有同样的抑制作用。当成纤维细胞与2.5微摩尔消炎痛预孵育时，AEC-CM的抑制作用完全逆转。此外，原代人AEC而非成纤维细胞分泌转化生长因子-β（TGF-β），且AEC-CM的抑制作用被中和性抗TGF-β抗体阻断。
这些结果表明，AEC通过TGF-β 主动抑制正常和纤维化成纤维细胞的增殖，TGF-β 可诱导成纤维细胞合成前列腺素E2。数据表明，增殖性肺部疾病可将上皮细胞作为药物作用靶点进行治疗。
