Six-transmembrane epithelial antigen of prostate 4 (STEAP4) is expressed on monocytes/neutrophils, and is regulated by TNF antagonist in patients with rheumatoid arthritis.
Six-transmembrane epithelial antigen of prostate 4 (STEAP4) is expressed on monocytes/neutrophils, and is regulated by TNF antagonist in patients with rheumatoid arthritis.
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发表时间：
2012
影响因子：
3.7
通讯作者：
Y. Tanaka;I. Matsumoto;K. Iwanami;A. Inoue;N. Umeda;Y. Tanaka;M. Sugihara;T. Hayashi;S. Ito;T. Sumida
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作者：
Y. Tanaka;I. Matsumoto;K. Iwanami;A. Inoue;N. Umeda;Y. Tanaka;M. Sugihara;T. Hayashi;S. Ito;T. Sumida
人前列腺六跨膜上皮抗原4（STEAP 4）是STEAP家族的成员之一，是小鼠肿瘤坏死因子-α诱导的脂肪相关蛋白（TIARP）的同源物。最近，我们报道了TIARP基因在葡萄糖-6-磷酸异构化酶（GPI）诱导的关节炎模型的脾脏和关节中的表达显著增加，提示其与关节炎的关系。本研究的目的是评估STEAP 4在类风湿关节炎（RA）患者外周血中的表达、定位和功能。方法采用流式细胞术检测7例RA患者外周血STEAP 4的表达。将中性粒细胞的数量与RA患者外周血来源的STEAP 4 mRNA的表达进行比较。将HL 60与维甲酸一起导入中性粒细胞，转染GFP-STEAP 4质粒DNA，用transwell法检测HL 60的迁移能力。另外，分析40例RA患者在英夫利西单抗治疗前后STEAP 4 mRNA的变化。结果STEAP 4在RA患者外周血单核细胞和中性粒细胞上均有表达。中性粒细胞数与STEAP 4 mRNA表达呈正相关。STEAP 4的过度表达下调了HL 60的迁移。STEAP 4 mRNA的表达在英夫利西单抗治疗后显著降低，尤其是在良好反应者中。结论STEAP 4表达于外周血单核细胞和中性粒细胞，调节细胞迁移，TNF拮抗剂可下调STEAP 4的表达，STEAP 4可能是TNF拮抗剂反应的预测因子。
OBJECTIVES Human six-transmembrane epithelial antigen of prostate 4 (STEAP4) is one of the STEAP family as a homologue of mouse tumour necrosis factor-α-induced adipose-related protein (TIARP). Recently, we reported that the TIARP gene expression was remarkably increased in spleen and joints of glucose-6-phosphate isomerise (GPI)-induced arthritis model, suggesting pivotal association to arthritis. The aim of the present study was to assess the expression, localisation and function of STEAP4 in peripheral blood of patients with rheumatoid arthritis (RA). METHODS Peripheral blood was obtained from seven patients with RA, the surface expression of STEAP4 was detected by flow cytometry. The number of neutrophils was compared with the expression of STEAP4 mRNA derived from peripheral blood of patients with RA. Neutrophils were introduced by HL60 with retinoic acid, and were transfected with GFP-STEAP4 plasmid DNA, then the migration of neutrophil-like HL60 was determined by transwell assay. In addition, the fluctuation of STEAP4 mRNA was analysed before and after treatment with infliximab in 40 patients with RA. RESULTS STEAP4 was expressed on monocytes and neutrophils in peripheral blood in RA. The number of neutrophils and expression of STEAP4 mRNA was positively correlated. Migration of neutrophil-like HL60 was down-regulated by over-expression of STEAP4. Expression of STEAP4 Mrna was significantly decreased after infliximab treatment in patients with RA, especially in good responders. CONCLUSIONS STEAP4 is expressed on monocytes and neutrophils in peripheral blood, regulates cell migration, is down-regulated by TNF antagonist, and might be a possible predictor of response to TNF antagonist.