Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-β and IL-10

Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-β and IL-10
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DOI:
10.1183/09031936.03.00014703
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发表时间:
2003-07-01
影响因子:
24.3
通讯作者:
Tazi, A
Tazi, A
中科院分区:
医学1区
文献类型:
--
作者:
Bergeron, A;Soler, P;Tazi, A

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细胞因子表达的调节是治疗特发性肺纤维化 (IPF) 的潜在有用方法。为了确定此类干预的潜在靶标,使用半定量逆转录酶聚合酶链反应比较了诊断时 IPF 患者和对照受试者肺组织中编码 17 种细胞因子的信使核糖核酸 (mRNA) 的表达。还通过免疫组织化学技术在蛋白质水平上研究了一些细胞因子。编码所有细胞因子的mRNA;在对照和纤维化肺样本中均检测到了评估的结果。与对照组相比,IPF 患者肺活检中只有转化生长因子 (TGF)-β 和白细胞介素 (IL)10 mRNA 定量增加,这一结果通过免疫组织化学在蛋白质水平得到证实。尽管血小板衍生生长因子 (PDGF)-BB 和角质形成细胞生长因子 (KGF) 的 mRNA 在 IPF 患者和对照患者的肺部表达量相似,但在 IPF 中也观察到这两种因子的局部积累。增生性肺泡上皮细胞是细胞因子的重要来源,其中 IL-10、PbGF-BB 和 KGF 的含量增加,但也观察到在成纤维细胞、平滑肌细胞和基质成分中积累增加(PDGF-BB、TGF-β)。这些结果为特发性肺纤维化中肺部产生的细胞因子提供了新的见解,并表明调节转化生长因子-β 和白介素-10 的产生可能代表一种潜在有用的方法。这种致残疾病的治疗策略。
Modulation of cytokine expression represents a potentially useful approach for the treatment of idiopathic pulmonary fibrosis (IPF).To identify potential targets for such intervention, semi-quantitative reverse transcriptase-polymerase chain reaction was used to compare the expression of messenger ribonucleic acids (mRNAs) coding for 17 cytokines in lung tissue obtained from patients with IPF at the time of diagnosis and control subjects. Some cytokines were also studied at the protein level by immunohistochemical techniques.mRNAs coding for all of the cytokines; evaluated were detected in both control and fibrotic lung samples. Only transforming growth factor (TGF)-beta and interleukin (IL)10 mRNAs were quantitatively increased in lung biopsies from patients with IPF compared with those of controls, results confirmed at the protein level by immunohistochemistry. Although mRNAs for platelet-derived growth factor (PDGF)-BB and keratinocyte growth factor (KGF) were expressed in similar amounts in lungs from patients with IPF and controls, localised accumulation of both factors was also observed in IPF. Hyperplastic alveolar epithelial cells were a prominent source of cytokines, where IL-10, PbGF-BB and KGF were present in increased amounts, although increased accumulation in fibroblasts, smooth-muscle cells and matrix components was also observed (PDGF-BB, TGF-beta).These results offer new insights into the cytokines produced in the lung in idiopathic pulmonary fibrosis and suggest that modulation of the production of transforming growth factor-beta and interleukin-10 may represent a potentially useful therapeutic strategy for this disabling disease.