Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis.
Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis.
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DOI：
10.1186/ar2779
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发表时间：
2009
影响因子：
4.9
通讯作者：
Sumida T
中科院分区：
文献类型：
--
作者：
Inoue A;Matsumoto I;Tanaka Y;Iwanami K;Kanamori A;Ochiai N;Goto D;Ito S;Sumida T
肿瘤坏死因子-α（TNFα）在类风湿性关节炎（RA）中起关键作用;然而，TNFα拮抗剂在RA中的作用机制尚不清楚。用葡萄糖-6-磷酸异构酶（GPI）免疫DBA/1小鼠诱导严重的急性关节炎。这种关节炎可以通过TNFα拮抗剂控制，提示与RA相似的病因。本研究旨在探讨TNFα在关节炎中的作用机制。首先，我们使用GPI诱导关节炎小鼠的脾细胞进行基因芯片分析。检测脾脏、关节和淋巴结中TNFα诱导的脂肪相关蛋白（TIARP）mRNA和蛋白的表达，并分析抗TNF α单克隆抗体（mAb）给药后TIARP mRNA的变化。还探讨了TIARP在脾脏和关节中的定位。还在人外周血单核细胞和滑膜中评价了前列腺六跨膜上皮抗原（STEAP）蛋白家族（TIARP基因的人直系同源物）。在TNFα相关基因中，TIARP mRNA的表达量最高，是对照组的20倍以上。在关节炎小鼠的关节和脾脏中特异性检测到TIARP mRNA，并且其在滑膜中的水平与关节肿胀的严重程度相关。用抗TNF mAb处理显著降低脾细胞中的TIARP mRNA表达。在脾细胞中，CD 11b+细胞是TIARP mRNA的主要来源。免疫组化显示TIARP蛋白主要定位于增生的滑膜中。在STEAP蛋白家族中，STEAP 4在RA患者的关节中高度上调，尤其是与CD 68+巨噬细胞共定位。结果揭示了TNFα拮抗剂在自身免疫性关节炎中的新作用机制，表明TIARP通过调节炎性细胞因子在炎性关节炎中发挥重要作用。
Tumor necrosis factor-alpha (TNFα) plays a pivotal role in rheumatoid arthritis (RA); however, the mechanism of action of TNFα antagonists in RA is poorly defined. Immunization of DBA/1 mice with glucose-6-phosphate isomerase (GPI) induces severe acute arthritis. This arthritis can be controlled by TNFα antagonists, suggesting similar etiology to RA. In this study, we explored TNFα-related mechanisms of arthritis. First, we performed GeneChip analysis using splenocytes of mice with GPI-induced arthritis. Expression of TNFα-induced adipose-related protein (TIARP) mRNA and protein in spleens, joints and lymph nodes was evaluated, and fluctuation of TIARP mRNA was analyzed after administration of anti-TNFα monoclonal antibody (mAb). Localization of TIARP in spleen and joints was also explored. Six-transmembrane epithelial antigen of the prostate (STEAP) families of proteins, the human ortholog of TIARP gene, were also evaluated in human peripheral blood mononucleocytes and synovium. Among the arrayed TNFα-related genes, the expression of TIARP mRNA was the highest (more than 20 times the control). TIARP mRNA was detected specifically in joints and spleens of arthritic mice, and their levels in the synovia correlated with severity of joint swelling. Treatment with anti-TNF mAb significantly reduced TIARP mRNA expression in splenocytes. Among the splenocytes, CD11b+ cells were the main source of TIARP mRNA. Immunohistochemistry showed that TIARP protein was mainly localized in hyperplastic synovium. Among the STEAP family of proteins, STEAP4 was highly upregulated in joints of patients with RA and especially co-localized with CD68+ macrophages. The results shed light on the new mechanism of action of TNFα antagonists in autoimmune arthritis, suggesting that TIARP plays an important role in inflammatory arthritis, through the regulation of inflammatory cytokines.
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影响因子：
8
作者：
Korkmaz, CG;Korkmaz, KS;Saatcioglu, F
通讯作者：
Saatcioglu, F
影响因子：
4.4
作者：
Schubert, D;Maier, B;Kamradt, T
通讯作者：
Kamradt, T
DOI：
10.1073/pnas.96.25.14523
发表时间：
1999-12-07
影响因子：
11.1
作者：
Hubert, RS;Vivanco, I;Afar, DEH
通讯作者：
Afar, DEH
影响因子：
3.8
作者：
Sanchez-Pulido L;Rojas AM;Valencia A;Martinez-A C;Andrade MA
通讯作者：
Andrade MA
影响因子：
4.8
作者：
Moldes, M;Lasnier, F;Chambaut-Guérin, AM
通讯作者：
Chambaut-Guérin, AM