Oncostatin M inhibits IL-1-induced expression of IL-8 and granulocyte-macrophage colony-stimulating factor by synovial and lung fibroblasts.
Oncostatin M inhibits IL-1-induced expression of IL-8 and granulocyte-macrophage colony-stimulating factor by synovial and lung fibroblasts.
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Oncostatin M 通过滑膜和肺成纤维细胞抑制 IL-1 诱导的 IL-8 和粒细胞巨噬细胞集落刺激因子的表达。
作者：
C. Richards;C. Langdon;F. Botelho;T. Brown;A. Agro
抑癌素M （OM）在结缔组织细胞调节细胞因子产生中的作用在很大程度上尚未被探索。我们研究了OM单独或与IL-1、IL-1 α（或IL-1 β）联合以1或5 ng/ml刺激来源于人滑膜和正常肺的成纤维细胞培养的效果，刺激产生高水平的粒细胞-巨噬细胞CSF （GM-CSF）、IL-8和IL-6蛋白。在不同浓度（0.1-50 ng/ml）下，单独使用OM刺激18 h后，不能显著提高GM-CSF、IL-8、IL-6或G-CSF的蛋白或mRNA水平。当与IL-1 α或- β联合使用时，OM引起IL-1诱导的IL-8和GM-CSF蛋白水平和mRNA表达的剂量依赖性抑制，而IL-6的产生同时增强。相反，当IL-6或白血病抑制因子（另外两种与OM共享gp130受体成分的细胞因子）以类似的方式与IL-1 α联合使用时，两种细胞因子都不能持续改变IL-1诱导的IL-8、GM-CSF或IL-6的水平。此外，电泳迁移量测定显示，在受刺激的成纤维细胞提取物中，只有OM而不是IL-6或白血病抑制因子能够诱导STAT-1核因子与DNA结合。这些结果表明，OM可以显著改变受刺激成纤维细胞的细胞因子谱，并可能在炎症部位这些细胞调节细胞因子的产生中发挥独特的作用。
The role of oncostatin M (OM) in modulating production of cytokines by connective tissue cells is largely unexplored. We have examined the effects of stimulating fibroblast cultures derived from human synovium and from normal lung with OM alone or in combination with IL-1, IL-1 alpha (or IL-1 beta) at 1 or 5 ng/ml, stimulated production of high levels of granulocyte-macrophage CSF (GM-CSF), IL-8, and IL-6 protein. At various concentrations (0.1-50 ng/ml), OM alone failed to significantly enhance protein or mRNA levels of GM-CSF, IL-8, IL-6, or G-CSF after 18 h of stimulation. When combined with IL-1 alpha or -beta, OM caused a dose-dependent inhibition of the IL-1-induced level of IL-8 and GM-CSF protein and mRNA expression, whereas IL-6 production was simultaneously enhanced. In contrast, when IL-6 or leukemia inhibitory factor (two other cytokines that share gp130 receptor components with OM) were used in a similar fashion in combination with IL-1 alpha, neither cytokine consistently altered the IL-1-induced levels of IL-8, GM-CSF, or IL-6. In addition, only OM and not IL-6 or leukemia inhibitory factor was able to induce STAT-1 nuclear factor binding to DNA in stimulated fibroblast extracts as measured by electrophoretic mobility shift assay. These results suggest that OM can significantly alter cytokine profiles of stimulated fibroblasts and may play a unique role in modulating cytokine production by these cells at sites of inflammation.