Specific overexpression of TNFAIP9 in CD14 CD16 monocytes in patients with rheumatoid arthritis：Comparative analysis with TNFAIP3
Specific overexpression of TNFAIP9 in CD14 CD16 monocytes in patients with rheumatoid arthritis：Comparative analysis with TNFAIP3
复制标题
类风湿性关节炎患者 CD14 CD16 单核细胞中 TNFAIP9 的特异性过表达：与 TNFAIP3 的比较分析
DOI：
10.1111/cei.12606
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Sumida T
中科院分区：
文献类型：
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作者：
Takai C;Matsumoto I;Inoue A;Umeda N;Tanaka Y;Kurashima Y;Wada Y;Narita I;Sumida T
肿瘤坏死因子-α诱导蛋白(TNFAIP9)和TNFAIP3在小鼠关节炎发病机制中起重要作用。为了阐明它们在类风湿关节炎(RA)患者中的病理生理作用，我们检测了它们在外周血单个核细胞(PBMC)中的表达和定位。检测类风湿关节炎患者和正常对照组PBMC中TNFAIP9和TNFAIP3的表达。用流式细胞术分析主要表达TNFAIP9和TNFAIP3的细胞群体。用肿瘤坏死因子α和脂多糖刺激体外培养的CD14+细胞，检测TNFAIP9和TNFAIP3mRNA的表达水平。分别于治疗前和治疗12周后检测TNFAIP9和TNFAIP3基因的表达水平。RA患者PBMC中TNFAIP9的表达显著高于对照组(P<0.05)，而TNFAIP3的表达低于对照组(P<0.05)。TNFAIP9表达于CD14+细胞，尤其是人类白细胞抗原D相关抗原(HLADR)+CD14brightCD16−细胞，而TNFAIP3主要表达于CD3+T细胞。肿瘤坏死因子-α和脂多糖在体外诱导人CD14+单核细胞表达TNFAIP9和TNFAIP3。用tocilizumab(n=13)治疗，而不是abatacept(n=11)治疗，可显著降低PBMC中TNFAIP9mRNA的表达，这与循环中CD14亮单核细胞的数量减少有关。CD14+细胞中TNFAIP9的表达在RA患者中呈特异性上调，受肿瘤坏死因子-α和脂多糖的调节，并被妥昔珠单抗抑制，而在PBMC中的表达呈现不同的定位和诱导模式。
The tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examinedin vitroon CD14+cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n= 36) than the control (n= 24) (eachP< 0·05). TNFAIP9 was expressed on CD14+cells, especially in human leucocyte antigen D-related (HLA-DR)+CD14brightCD16−cells, while TNFAIP3 was expressed mainly on CD3+T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14+monocytesin vitro. Treatment with tocilizumab (n= 13), but not abatacept (n= 11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14brightmonocytes. The expression of TNFAIP9 in CD14+cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.