Radiation-induced pulmonary fibrosis: Examination of chemokine and chemokine receptor families
Radiation-induced pulmonary fibrosis: Examination of chemokine and chemokine receptor families
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DOI：
10.1667/0033-7587(2002)157
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发表时间：
2002-03-01
影响因子：
3.4
通讯作者：
Finkelstein, JN
中科院分区：
文献类型：
--
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
纤维化是慢性炎症或损伤的常见结果。肺纤维化可能是急性炎症反应后异常修复的结果。由组织损伤引发的修复过程在很大程度上是细胞活化以产生重要的生物介质如细胞因子、生长因子和趋化因子的功能，其协调炎症反应的大多数方面。因此，损伤和修复后炎性细胞因子和趋化因子的产生调节改变可能有助于纤维化。我们的假设是，在胸部照射诱导的纤维化阶段，特异性趋化因子和趋化因子受体的慢性表达可能会使淋巴细胞和巨噬细胞的募集和激活永久化，这可能有助于纤维化的发展。对纤维化敏感（C57 BL/6）和纤维化抗性（C3 H/HeJ）小鼠胸部进行单次剂量12.5戈伊照射。使用微阵列分析和RNA酶保护测定制备和杂交总肺RNA。在辐射后26周，编码趋化因子BLC的信息（现在称为Scyb 13），C10（现在称为Scya 6），IP-10（现在称为Scyb 10），MCP-1（现在称为Scya 2），MCP-3（现在称为Scya 7），MIP-1gamma（现在称为Scya 9）和RANTES（现在称为Scya 5）以及趋化因子受体Ccr 1、Ccr 2、Ccr 5和Ccr 6在纤维化敏感（C57 BL/6）小鼠中升高。相比之下，只有编码SDF-1 α（现在称为Sdf 1）和Ccr 1的信息在纤维化抗性（C2 H/HeJ）小鼠中放射后26周升高。我们的研究结果指出CC和CCR家族成员作为纤维化发展过程中的主要趋化因子应答者。这些研究表明，单核细胞/巨噬细胞和淋巴细胞的募集和激活是辐射诱导的纤维化的关键组成部分。(C)2002年，辐射研究协会。
Fibrosis is a common outcome of chronic inflammation or injury. Pulmonary fibrosis may be the result of abnormal repair after an acute inflammatory response. The process of repair initiated by a tissue insult is largely a function of the activation of cells to produce important biological mediators such as cytokines, growth factors and chemokines, which orchestrate most aspects of the inflammatory response. Consequently, altered regulation of the production of inflammatory cell cytokines and chemokines after injury and repair likely contributes to the fibrosis. Our hypothesis is that chronic expression of specific chemokine and chemokine receptors during the fibrotic phase induced by thoracic irradiation may perpetuate the recruitment and activation of lymphocytes and macrophages, which may contribute to the development of fibrosis. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized using microarray analysis and RNase protection assays. At 26 weeks postirradiation, messages encoding the chemokines BLC (now known as Scyb13), C10 (now known as Scya6), IP-10 (now known as Scyb10), MCP-1 (now known as Scya2), MCP-3 (now known as Scya7), MIP-1gamma (now known as Scya9), and RANTES (now known as Scya5) and the chemokine receptors Ccr1, Ccr2, Ccr5 and Ccr6 were elevated in fibrosis-sensitive (C57BL/6) mice. In contrast, only the messages encoding SDF-1alpha (now known as Sdf1) and Ccr1 were elevated 26 weeks postirradiation in fibrosis-resistant (C2H/HeJ) mice. Our results point to the CC and CCR family members as the predominant chemokine responders during the development of fibrosis. These studies suggest that monocyte/macrophage and lymphocyte recruitment and activation are key components of radiation-induced fibrosis. (C) 2002 by Radiation Research Society.