Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis.
Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis.
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DOI：
10.4049/jimmunol.152.7.3606
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发表时间：
1994-04
影响因子：
4.4
通讯作者：
G. Sempowski;M. Beckmann;Stephen Derdak;R. Phipps
中科院分区：
文献类型：
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作者：
G. Sempowski;M. Beckmann;Stephen Derdak;R. Phipps
本研究的目的是确定小鼠肺成纤维细胞的分离亚群是否表达膜结合和可溶形式的IL-4受体，并评估IL-4受体触发的潜在功能后果。最近的研究表明，IL-4合成的Th 2细胞和肥大细胞在炎症和纤维化过程中在肺中以增加的数量存在，这表明IL-4可能在这些事件中起调节作用。我们假设肺成纤维细胞及其亚群密切参与这种炎症反应，并且IL-4是刺激成纤维细胞胶原蛋白合成和过度增殖的积极参与者，在肺中产生纤维化环境。这些实验中使用的成纤维细胞亚群不仅在胸腺细胞-1（Thy-1）Ag的表面表达方面不同，而且在功能和形态上也不同。我们现在报告的新发现，IL-4受体是目前在不一致的水平对Thy-1+和Thy-1-肺成纤维细胞。使用单克隆抗IL-4 R Ab和125 I标记的IL-4的平衡结合分析来分析IL-4 R水平和亲和力。逆转录PCR显示存在膜结合和可溶性IL-4 R的mRNA。肺成纤维细胞亚群以显著不同的水平分泌可溶性IL-4 R蛋白，如通过ELISA检测的。用IL-4处理Thy-1+和Thy-1-肺成纤维细胞以确定该细胞因子是否是促纤维化的。Thy-1+成纤维细胞通过增殖和上调胶原蛋白的产生来响应IL-4。相比之下，Thy-1-成纤维细胞增殖的程度低于Thy-1+成纤维细胞，并且未被刺激以分泌增加水平的胶原。总体而言，这些结果表明，在损伤部位IL-4水平升高可通过增强成纤维细胞亚群增殖和胶原合成导致纤维化的发展。
The purpose of this study was to determine whether or not membrane-bound and soluble forms of IL-4 receptors are expressed by isolated subsets of murine lung fibroblasts and to evaluate the potential functional consequences of IL-4 receptor triggering. Recent studies demonstrate that IL-4-synthesizing Th2 cells and mast cells are present in increased numbers in the lung during inflammation and fibrosis, suggesting that IL-4 may play a regulatory role in these events. We hypothesize that pulmonary fibroblasts and subsets thereof are intimately involved in this inflammatory response and that IL-4 is an active player in stimulating fibroblast collagen synthesis and hyperproliferation, creating a fibrotic environment in the lung. The fibroblast subsets used in these experiments differ not only in surface expression of the thymocyte-1 (Thy-1) Ag, but also in function and morphology. We now report the novel finding that IL-4 receptors are present at discordant levels on Thy-1+ and Thy-1- lung fibroblasts. IL-4R level and affinity were analyzed using a monoclonal anti-IL-4R Ab and equilibrium binding analysis with 125I-labeled IL-4. Reverse transcriptase PCR demonstrated the presence of mRNA for membrane-bound and soluble IL-4R. Lung fibroblast subsets secrete soluble IL-4R protein at dramatically different levels, as detected by an ELISA. Thy-1+ and Thy-1- lung fibroblasts were treated with IL-4 to determine whether this cytokine was profibrotic. Thy-1+ fibroblasts responded to IL-4 by proliferating and up-regulating collagen production. In contrast, Thy-1- fibroblasts proliferate to a lesser degree than Thy-1+ fibroblasts and were not stimulated to secrete increased levels of collagen. Overall, these results suggest that elevated levels of IL-4 at a site of injury could result in the development of fibrosis by enhancing fibroblast subset proliferation and collagen synthesis.