Department of Pneumology, CHU Liege, I3 GIGA Research, University of Liege, Avenue de l'hopital, 4000 Liège, Sart Tilman, Belgium.
Cytokine. 2017 Nov;99:1-8. doi: 10.1016/j.cyto.2017.06.018. Epub 2017 Jun 29.
Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by a profound airway remodelling that leads to airway obstruction. A role for transforming growth factor-β1 (TGF-β1) has been proposed in airway remodelling of COPD. Regarding the TGF-β1 production at local level, the results seemed to be controversial. In this study, an original model of sputum cell culture thought to maintain important cells interactions, was used. We investigated the production of TGF-β1 from sputum cell culture in 33 COPD encompassing the whole severity spectrum and compared the results with those found in 39 healthy controls. Sputum was induced by inhalation of saline, the cellular fraction cultured for 24 h and the spontaneous production of total TGF-β1 was assessed by ELISA. Using, a TGF-β1 reporter cell assay, we also compared the levels of active and total TGF-β1 in the sputum cell culture supernatants of COPD and controls. Moreover, as a combination of tumor necrosis factor-α (TNF-α) and TGF-β1 have been shown to have a cumulative impact on the severity of airflow limitation in COPD, the TNF-α release was also measured in a representative subgroup of patients. Our results indicated that the use of sputum cell culture was a reliable and reproducible method to assess TGF-β1 production at airway level. Sputum cells from COPD produced greater amount of total TGF-β1 than those of healthy controls (p<0.001). This result was confirmed using the cell reporter assay which also showed a higher level of active TGF-β1 in the COPD group compared to controls. In addition, total TGF-β1 production was increased according to GOLD stage and was inversely related to FEV1/FVC ratio (p<0.05). By contrast, the production of this growth factor was not correlated with the functional markers of emphysema nor with demographic characteristics such as age, BMI or smoking status. Interestingly, the production of total TGF-β1 was inversely related to that of TNF-α (r=-0.53, p<0.05) which was decreased in COPD. In summary, COPD patients displayed a raised production of total and active TGF-β1 from their airway cells. Total TGF-β1 correlates with the severity of airway obstruction without evidence of a link with emphysema. .
慢性阻塞性肺疾病（COPD）是一种慢性气道疾病，其特征为气道重塑导致气道阻塞。转化生长因子-β1（TGF-β1）在 COPD 的气道重塑中起作用。关于局部水平的 TGF-β1 产生，结果似乎存在争议。在这项研究中，使用了一种被认为可以维持重要细胞相互作用的痰液细胞培养的原始模型。我们调查了 33 例 COPD 患者痰液细胞培养中 TGF-β1 的产生，并将结果与 39 例健康对照者进行了比较。通过吸入生理盐水诱导痰液，培养细胞 24 小时，并通过 ELISA 评估总 TGF-β1 的自发产生。使用 TGF-β1 报告细胞测定法，我们还比较了 COPD 和对照组痰液细胞培养上清液中活性和总 TGF-β1 的水平。此外，由于 TNF-α（TNF-α）和 TGF-β1 的组合已被证明对 COPD 气流受限的严重程度具有累积影响，因此在具有代表性的患者亚组中还测量了 TNF-α 的释放。我们的结果表明，痰液细胞培养是一种可靠且可重复的方法，可评估气道水平的 TGF-β1 产生。COPD 患者的痰液细胞产生的总 TGF-β1量多于健康对照组（p<0.001）。该结果使用细胞报告测定法得到了证实，该测定法还显示 COPD 组中活性 TGF-β1 的水平高于对照组。此外，总 TGF-β1 的产生随着 GOLD 分期而增加，与 FEV1/FVC 比值呈负相关（p<0.05）。相比之下，该生长因子的产生与肺气肿的功能标志物或年龄、BMI 或吸烟状况等人口统计学特征无关。有趣的是，总 TGF-β1 的产生与 TNF-α 的产生呈负相关（r=-0.53，p<0.05），而 COPD 患者的 TNF-α 减少。总之，COPD 患者的气道细胞总 TGF-β1 和活性 TGF-β1 的产生增加。总 TGF-β1 与气道阻塞的严重程度相关，与肺气肿无关。
