Hamilton J A, Waring P M, Filonzi E L
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
J Immunol. 1993 Feb 15;150(4):1496-502.
The cytokines, IL-1 alpha and TNF-alpha, induced a dose-dependent production of leukemia inhibitory factor (LIF) in cultured human synovial fibroblast-like cells, as measured by a radioreceptor competition assay. Significant levels of LIF were first detected in cell supernatants between 2 and 4 h after cytokine addition. Increases were also observed in LIF mRNA steady-state expression. Evidence is presented for down-regulation of the IL-1-induced LIF activity by an endogenous cyclo-oxygenase product(s); the glucocorticoid, dexamethasone, lowered the IL-1-induced LIF activity and mRNA expression. A synergistic effect was noted between the actions of IL-1 alpha and TNF-alpha, and between IL-1 and transforming growth factor-beta. IFN-gamma could not induce LIF formation in the synovial cells but inhibited the stimulatory effect of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular LIF production in the joints of patients with inflammatory arthritis. Synoviocyte-derived LIF may activate monocyte/macrophages in the lesions and may contribute to the bone changes and certain systemic manifestations in patients with inflammatory joint disease.
通过放射受体竞争分析测定，细胞因子白细胞介素-1α（IL-1α）和肿瘤坏死因子-α（TNF-α）可在培养的人滑膜成纤维样细胞中诱导白血病抑制因子（LIF）产生呈剂量依赖性。在添加细胞因子后2至4小时之间，首次在细胞上清液中检测到显著水平的LIF。LIF mRNA稳态表达也有增加。有证据表明内源性环氧化酶产物可下调IL-1诱导的LIF活性；糖皮质激素地塞米松降低了IL-1诱导的LIF活性和mRNA表达。注意到IL-1α与TNF-α的作用之间，以及IL-1与转化生长因子-β之间存在协同效应。干扰素-γ（IFN-γ）不能在滑膜细胞中诱导LIF形成，但抑制了IL-1的刺激作用。这些结果表明，细胞因子刺激的滑膜成纤维细胞可能是炎性关节炎患者关节内LIF产生的主要来源。滑膜细胞衍生的LIF可能激活病变中的单核细胞/巨噬细胞，并可能导致炎性关节病患者的骨质改变和某些全身表现。
