Tumor necrosis factor-α increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint

Tumor necrosis factor-α increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint
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DOI:
10.1111/j.1600-0714.2005.00302.x
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发表时间:
2005-07-01
影响因子:
3.3
通讯作者:
Kondoh, T
Kondoh, T
中科院分区:
医学3区
文献类型:
--
作者:
Ogura, N;Tobe, M;Kondoh, T

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背景:以炎性细胞浸润为特征的滑膜炎常伴随着颞下颌关节(TMJ)临床症状的进展。TMJ的滑膜成纤维细胞被认为在滑膜炎的进展中起着重要作用。本研究旨在检测肿瘤坏死因子-α(TNF-α)刺激的滑膜成纤维细胞趋化因子的产生和基因表达。方法:采用酶联免疫吸附试验(ELISA)检测滑膜成纤维细胞趋化因子的蛋白水平。结果:TNF-α可促进滑膜成纤维细胞产生IL-8、Gro-α、单核细胞趋化蛋白(MCP)-1和活化调节正常T细胞表达与分泌(RANTES)蛋白。在滑膜成纤维细胞的条件培养液中,未检测到基质细胞衍生因子(SDF)-1α、巨噬细胞炎症蛋白(MIP)-1α和-1β的表达。IL-8、Gro-α、MCP-1和RANTES的基因表达随着肿瘤坏死因子-α的治疗而增加。结论:滑膜成纤维细胞在肿瘤坏死因子治疗后的蛋白合成和趋化因子的基因表达增加,在炎症细胞向滑膜的募集和滑膜炎症的进展中起着重要作用。
BACKGROUND: Synovitis, which is characterized by infiltration of inflammatory cells, often accompanies progression of clinical symptoms of the temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to play important roles in progression of synovitis. The purpose of this study was to examine production and gene expression of chemokines by synovial fibroblasts stimulated by tumor necrosis factor-alpha (TNF-alpha).METHODS: Protein levels of chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of chemokines was analyzed by real-time polymerase chain reaction (PCR).RESULTS: Production of interleukin (IL)-8, growth-related oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1 alpha, macrophage inflammatory protein (MIP)-1 alpha and -1 beta were not detectable in conditioned media of synovial fibroblasts, with or without TNF-alpha treatment. Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to TNF-alpha treatment were detected.CONCLUSIONS: Increased protein production and gene expression of chemokines by synovial fibroblasts in response to TNF-alpha treatment appears to play an important role in recruitment of inflammatory cells into synovium and the progression of synovitis in the TMJ.