Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia
Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia
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DOI：
10.1016/s0002-9440(10)63759-5
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发表时间：
2004-06-01
影响因子：
6
通讯作者：
Hogaboam, CM
中科院分区：
文献类型：
--
作者：
Jakubzick, C;Choi, ES;Hogaboam, CM
肺成纤维细胞的异常增殖是慢性肺纤维化疾病如特发性间质性肺炎（IIp）的突出特征，但目前尚不清楚如何治疗性调节肺成纤维细胞的这种增殖反应。在本研究中，我们研究了是否有可能选择性靶向原发性人肺成纤维细胞生长的手术肺活检（SLB）从HP患者的白细胞介素-4受体（IL-4 R）和IL-13 R亚基的表达的基础上。与从其他IIP SLB和正常SLB生长的原代肺成纤维细胞系相比，从最严重形式的HP（即普通型间质性肺炎）患者培养的肺成纤维细胞系显示出IL-4 R α、IL-13 Ra 1和IL-13 Ra 2的最大基因和蛋白表达。当暴露于增加浓度的由人IL-13和截短形式的假单胞菌外毒素（IL 13-PE）组成的嵌合蛋白时，与来自非特异性间质性肺炎和呼吸性细支气管炎/间质性肺病患者组的成纤维细胞系相比，原发性普通型间质性肺炎成纤维细胞的增殖受到更大程度的抑制。来自正常患者的成纤维细胞对IL 13-PE的细胞毒性作用表现出最小的易感性。IL-13-PE介导的UP成纤维细胞的靶向依赖于它们的IL-4 Ra和IL-13 Ra 2的表达。因此，这些数据表明，来自某些IIP患者组的人肺成纤维细胞的异常增殖特性可以以依赖于这些细胞的IL-4和IL-13受体亚基表达的方式调节。
Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIp), but it is not presently clear how this proliferative response by lung fibroblasts can be therapeutically modulated. In the present study, we examined whether it was possible to selectively target primary human pulmonary fibroblasts grown out of surgical lung biopsies (SLBs) from HP patients based on their expression of interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines cultured from patients with the severest form of HP, namely usual interstitial pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines grown from other IIP SLBs and normal SLBs. When exposed to increasing concentrations of a chimeric protein comprised of human IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual interstitial pneumonia fibroblasts was inhibited to a much greater extent compared with fibroblast lines from nonspecific interstitial pneumonia and respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts from normal patients exhibited minimal susceptibility to the cytotoxic effect of IL13-PE. IL13-PE-mediated targeting of UP fibroblasts was dependent on their expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the abnormal proliferative properties of human lung fibroblasts from certain IIP patient groups can be modulated in a manner that is dependent on the IL-4 and IL-13 receptor subunit expression by these cells.