Silvera M R, Phipps R P
University of Rochester Cancer Center, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
J Interferon Cytokine Res. 1995 Jan;15(1):63-70. doi: 10.1089/jir.1995.15.63.
IL-1 is a key cytokine that promotes pulmonary inflammation and fibrosis, as a result of its ability to stimulate lung fibroblast proliferation and collagen synthesis, two hallmarks of fibrosis. The IL-1 receptor antagonist (IL-1Ra) is an important natural inhibitor of IL-1-mediated functions. In models of pulmonary fibrosis induced by chemotherapeutic agents or noxious particles, administration of IL-1Ra significantly ameliorates lung fibrosis. Lung tissue undergoing an inflammatory response shows elevations in IL-1Ra, although it is not clear which pulmonary cells are responsible for the IL-1Ra synthesis. The purpose of this research was to determine whether Thy-1+ and Thy-1- subsets of mouse lung fibroblasts were capable of synthesizing IL-1Ra. In this report, it is demonstrated for the first time that lung fibroblasts are capable of synthesizing IL-1Ra. Both Thy-1+ and Thy-1- parental lines and clones constitutively express IL-1Ra mRNA. Quantitation of IL-1Ra protein indicates that Thy-1+ and Thy-1- fibroblasts secrete similar levels of secreted but not intracellular IL-1Ra. Thy-1- fibroblasts accumulate higher levels of IL-1Ra intracellularly. Moreover, fibroblast-conditioned supernatants containing IL-1Ra significantly suppress the mitogenic response of a T cell clone, D10G4.1, to concanavalin A and IL-1 beta. Overall, our observations indicate that Thy-1+ and Thy-1- fibroblasts release IL-1Ra and possess an IL-1-specific inhibitory activity in their supernatants. In vivo, fibroblast-derived IL-1Ra may serve to regulate IL-1-mediated effects in an autocrine and/or paracrine fashion to maintain homeostasis in the pulmonary interstitium.
白细胞介素 -1（IL-1）是一种关键的细胞因子，因其能够刺激肺成纤维细胞增殖和胶原蛋白合成（纤维化的两个标志）而促进肺部炎症和纤维化。白细胞介素 -1受体拮抗剂（IL-1Ra）是IL-1介导功能的重要天然抑制剂。在化疗药物或有害颗粒诱导的肺纤维化模型中，给予IL-1Ra可显著改善肺纤维化。经历炎症反应的肺组织中IL-1Ra水平升高，尽管尚不清楚哪些肺细胞负责IL-1Ra的合成。本研究的目的是确定小鼠肺成纤维细胞的Thy-1 +和Thy-1 -亚群是否能够合成IL-1Ra。在本报告中，首次证明肺成纤维细胞能够合成IL-1Ra。Thy-1 +和Thy-1 -亲代细胞系及克隆均组成性表达IL-1Ra mRNA。对IL-1Ra蛋白的定量分析表明，Thy-1 +和Thy-1 -成纤维细胞分泌的分泌型IL-1Ra水平相似，但细胞内IL-1Ra水平不同。Thy-1 -成纤维细胞在细胞内积累更高水平的IL-1Ra。此外，含有IL-1Ra的成纤维细胞条件上清液可显著抑制T细胞克隆D10G4.1对伴刀豆球蛋白A和IL-1β的促有丝分裂反应。总体而言，我们的观察结果表明，Thy-1 +和Thy-1 -成纤维细胞释放IL-1Ra，并在其上清液中具有IL-1特异性抑制活性。在体内，成纤维细胞衍生的IL-1Ra可能以自分泌和/或旁分泌方式调节IL-1介导的效应，以维持肺间质的稳态。
