Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis
Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis
复制标题
DOI：
10.1165/rcmb.2002-0009oc
复制
发表时间：
2002-10-01
影响因子：
6.4
通讯作者：
Keane, MP
中科院分区：
文献类型：
--
作者：
Belperio, JA;Dy, M;Keane, MP
炎症细胞募集的初始刺激和慢性炎症、肉芽组织形成和纤维化的持续和演变机制尚未完全阐明。虽然白细胞介素（IL）-13（Th 2细胞因子）已被证明对支持纤维增殖的成纤维细胞具有直接作用，但它也是一种新型CC趋化因子C10的有效诱导剂，C10对单核吞噬细胞具有趋化性。巨噬细胞/单核吞噬细胞已被证明在肺纤维化的发病机制中具有作用，作为调节细胞外基质合成的生长因子的重要来源。在这项研究中，我们证明了IL-13和C10在博莱霉素诱导的肺纤维化的发病机制中升高。中和IL-13而非IL-4可减弱博莱霉素诱导的肺纤维化和C10水平，表明IL-13在肺纤维化的发展中具有重要作用。IL-13是体内C10的有效诱导剂，中和C10可减弱博莱霉素诱导的肺纤维化和肺内巨噬细胞数量。这表明IL-13在肺纤维化的发展中具有独立于其对成纤维细胞的直接作用的作用，并且是Th 2细胞因子和特异性CC趋化因子之间相互作用的证据。
The initial stimulus for inflammatory cell recruitment and the mechanisms responsible for the perpetuation and evolution of chronic inflammation, granulation tissue formation, and fibrosis have not been fully elucidated. Although interleukin (IL)-13, a Th2 cytokine, has been shown to have direct effects on fibroblasts that support fibroproliferation, it is also a potent inducer of a novel CC chemokine, C10, which is chemotactic for mononuclear phagocytes. The macrophage/mononuclear phagocyte has been shown to have a role in the pathogenesis of pulmonary fibrosis, serving as an important source of growth factors that regulate extracellular matrix synthesis. In this study we demonstrate that IL-13 and C10 are elevated in the pathogenesis of bleomycin-induced pulmonary fibrosis. Neutralization of IL-13, but not IL-4, attenuated bleomycin-induced pulmonary fibrosis and levels of C10, suggesting that IL-13 has an important role in the development of pulmonary fibrosis. IL-13 is a potent inducer of C10 in vivo, and neutralization of C10 attenuated bleomycin-induced pulmonary fibrosis and intrapulmonary macrophage numbers. This suggests that IL-13 has a role in the development of pulmonary fibrosis that is independent of its direct effect on fibroblasts and is evidence for an interaction between Th2 cytokines and specific CC chemokines.