LEUKEMIA INHIBITORY FACTOR IS EXPRESSED IN CARTILAGE AND SYNOVIUM AND CAN CONTRIBUTE TO THE PATHOGENESIS OF ARTHRITIS
LEUKEMIA INHIBITORY FACTOR IS EXPRESSED IN CARTILAGE AND SYNOVIUM AND CAN CONTRIBUTE TO THE PATHOGENESIS OF ARTHRITIS
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DOI：
10.1172/jci115964
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发表时间：
1992-09-01
影响因子：
15.9
通讯作者：
VILLIGER, PM
中科院分区：
文献类型：
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作者：
LOTZ, M;MOATS, T;VILLIGER, PM
这项研究报告了人类关节结缔组织中的白血病抑制因子（LIF）。具有生物活性的 LIF 存在于骨关节炎患者的滑液中，并且在类风湿性关节炎患者的样本中含量较高。培养的人滑膜细胞和关节软骨细胞产生具有生物活性的 LIF，并合成和分泌 LIF 蛋白，这些蛋白在 SDS PAGE 中以大约 43 kD 的速度迁移。用 IL-1-β 刺激后，该值增加。含血清培养物中的软骨细胞表达 4.2-kb LIF mRNA。 IL-1-β、LPS 以及较小程度的肿瘤坏死因子-α 诱导 LIF 基因表达。 LIF 自动诱导其 mRNA，这为该细胞因子对关节组织细胞功能的影响提供了证据。在测试的一系列生长因子中，转化生长因子（TGG-β），包括异构体 TGF-β-1、TGF-β-2 和 TGF-β-3、血小板源性生长因子、碱性成纤维细胞生长因子和胰岛素样生长因子诱导这种细胞因子基因，但其作用持续时间不同。培养的滑膜细胞表达 LIF 基因以响应同一组肽调节因子。信号转导途径分析表明，PMA 增加了 LIF mRNA，而钙离子载体和 cAMP 没有可检测到的影响。 Cycloheximide 是一种有效的 LIF mRNA 诱导剂，地塞米松可抑制 PMA 或 IL-1-β 诱导的 LIF。原位杂交证明，用 IL-1 刺激的软骨器官培养物和滑膜组织表达高水平的 LIF mRNA。这些结果表明 LIF 是一种由关节组织细胞产生的新细胞因子，在关节炎中过度表达。关节炎症期间存在的因子诱导这种细胞因子以及 LIF 对结缔组织细胞的影响表明 LIF 是一种可能促进关节炎发病机制的介质。
This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1-beta.Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1-beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGG-beta), including the isoforms TGF-beta-1, TGF-beta-2, and TGF-beta-3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1-beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization.These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis.