Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.
Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.
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DOI：
10.4049/jimmunol.150.9.4188
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发表时间：
1993-05
影响因子：
4.4
通讯作者：
Yihong Zhang;T. Lee;B. Guillemin;Ming-Chih Yu;W. Rom
中科院分区：
文献类型：
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作者：
Yihong Zhang;T. Lee;B. Guillemin;Ming-Chih Yu;W. Rom
特发性肺纤维化（IPF）和石棉肺是纤维化间质性肺疾病，其特征是肺泡壁纤维化，伴有细胞外基质积聚、间质重塑和活化肺泡巨噬细胞数量增加。动物模型和体外研究表明，巨噬细胞细胞因子，即IL-1β和TNF-α，在纤维化的发展中发挥重要作用。我们发现与正常对照相比，两种疾病中 TNF-α 的释放显着增加 (p < 0.01)，而石棉沉滞症中 IL-1 β 的释放显着增加 (p < 0.01)。此外，与正常人相比，IPF 或石棉沉滞症患者的肺泡巨噬细胞中这些细胞因子的 mRNA 表达增加。巨噬细胞上清液中 TNF-α 的释放水平与每毫升支气管肺泡灌洗液中返回的中性粒细胞数量相关。温石棉、青石棉、铁石棉和二氧化硅刺激 IL-1 β 和 TNF-α 释放，并上调巨噬细胞或单核细胞中各自的 mRNA。为了评估 IL-1β 和 TNF-α 在细胞外基质积累中的作用，我们研究了短期（2 小时）无血清暴露于重组细胞因子后人二倍体肺成纤维细胞中 I 型和 III 型胶原蛋白以及纤连蛋白基因的表达。两种细胞因子均将这些基因上调 1.5 至 3.6 倍。这些细胞因子有可能影响 IPF 和石棉肺下呼吸道的重塑和纤维化。
Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.