Nerve Growth Factor Regulation by TNF-α and IL-1β in Synovial Macrophages and Fibroblasts in Osteoarthritic Mice.

Nerve Growth Factor Regulation by TNF-α and IL-1β in Synovial Macrophages and Fibroblasts in Osteoarthritic Mice.
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DOI:
10.1155/2016/5706359
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发表时间:
2016
影响因子:
4.1
通讯作者:
Takaso M
Takaso M
中科院分区:
医学3区
文献类型:
--
作者:
Takano S;Uchida K;Miyagi M;Inoue G;Fujimaki H;Aikawa J;Iwase D;Minatani A;Iwabuchi K;Takaso M

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为了研究巨噬细胞在骨关节炎(OA)关节滑膜组织(ST)中作为神经生长因子(NGF)的调节者和生产者的作用,对OA小鼠(STR/Ort)ST中几种炎性细胞因子的基因表达谱进行了表征。具体而言,使用实时聚合酶链反应分析评价从小鼠OA模型ST分离的CD 11b+和CD 11b-细胞中肿瘤坏死因子-(TNF-)α、白细胞介素-(IL-)1β、IL-6和NGF的表达。观察TNF-α、IL-1β和IL-6对滑膜细胞NGF表达的影响。STR/Ort小鼠ST中TNF-α、IL-1β、IL-6和NGF的表达均高于C57/BL 6 J小鼠。与CD 11b-细胞组分相比,在CD 11b+细胞组分中检测到更高的TNF-α、IL-1β和IL-6表达水平,而在两种细胞组分之间检测到NGF表达无差异。值得注意的是,TNF-α上调滑膜成纤维细胞和巨噬细胞中的NGF表达,IL-1β上调滑膜成纤维细胞中的NGF表达。IL-1β和TNF-α可能调节OA关节内的NGF信号,是治疗OA疼痛的合适靶点。
To investigate the role of macrophages as a regulator and producer of nerve growth factor (NGF) in the synovial tissue (ST) of osteoarthritis (OA) joints, the gene expression profiles of several inflammatory cytokines in the ST, including synovial macrophages and fibroblasts, of OA mice (STR/Ort) were characterized. Specifically, real-time polymerase chain reaction analysis was used to evaluate the expression of tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and NGF in CD11b+ and CD11b– cells isolated from the ST of a murine OA model. The effects of TNF-α, IL-1β, and IL-6 on the expression of NGF in cultured synovial cells were also examined. The expression of TNF-α, IL-1β, IL-6, and NGF in the ST of STR/Ort was higher than that in C57/BL6J mice. Compared to the CD11b– cell fraction, higher expression levels of TNF-α, IL-1β, and IL-6 were detected in the CD11b+ cell fraction, whereas no differences in the expression of NGF were detected between the two cell fractions. Notably, TNF-α upregulated NGF expression in synovial fibroblasts and macrophages and IL-1β upregulated NGF expression in synovial fibroblasts. IL-1β and TNF-α may regulate NGF signaling in OA joints and be suitable therapeutic targets for treating OA pain.
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