Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus.
Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus.
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Olf1/EBF 相关锌指蛋白干扰系统性红斑狼疮患者抗核抗体的产生
DOI：
10.1186/ar2972
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发表时间：
2010
影响因子：
4.9
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Feng X;Li R;Huang J;Zhang H;Zhu L;Hua B;Tsao BP;Sun L
本研究的目的是确定Olf 1/EBF相关的锌指蛋白（OAZ），一种由位置性系统性红斑狼疮（SLE）候选基因编码的转录因子，在SLE的发病机制中起着重要作用。方法采用实时定量聚合酶链反应（qPCR）测定外周血细胞（PBL）中的基因表达水平。评估与疾病活动性和特异性自身抗体存在的相关性。将外周血单核细胞（PBMC）与特异性siRNA孵育三天，然后收获细胞用于使用qPCR测量mRNA水平，并使用ELISA测量上清液中总免疫球蛋白（IG）G和IgM以及分泌的细胞因子、趋化因子和抗核抗体（ANA）的水平。结果40例ANA阳性SLE患者外周血淋巴细胞OAZ基因表达水平明显高于30例正常对照组（P< 0.0001）和18例类风湿关节炎患者（P< 0.01）。SLE患者OAZ基因表达水平与SLE疾病活动指数（SLEDAI）评分呈正相关（r = 0.72，P < 0.0001），抗dsDNA抗体和抗Sm抗体阳性者OAZ基因表达水平更高（均P < 0.05）。与非靶向siRNA共培养相比，OAZ siRNA共培养使OAZ mRNA水平降低74.6 ± 6.4%，OAZ沉默导致培养上清液中总IgG、ANA、干扰素（IFN）-γ、白细胞介素（IL）-10、IL-12和IL-21水平降低，但CCL 2水平升高（P< 0.05）。ANA水平下降与OAZ表达抑制（r = 0.88，P = 0.05）、IL-21水平降低（r = 0.99，P < 0.01）、趋化因子配体2水平升高（r =-0.98，P < 0.01）相关。OAZ沉默后ID 1 -3表达分别下调68.7%、70.2%和67.7（P< 0.0001）并与疾病活动性相关结论SLE患者外周血淋巴细胞OAZ转录本的表达与疾病活动性密切相关。抑制OAZ表达可抑制下游ID水平，以及ANA和IL-21的分泌，提示OAZ通路在SLE发病机制中的作用。
IntroductionThe aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE.MethodsGene expression levels in peripheral blood cells (PBLs) measured using quantitative real-time polymerase chain reaction (qPCR) were assessed for association with disease activity and the presence of specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were incubated with specific siRNAs for three days, then cells were harvested for measuring mRNA levels using qPCR, and supernatants for levels of total immunoglobulin (Ig)G and IgM as well as secreted cytokines, chemokine and antinuclear antibodies (ANA) using ELISA. Indirect immunofluorescence was also applied for ANA detection.ResultsOAZ gene expressions in PBLs from 40 ANA-positive SLE patients were significantly increased than those from 30 normal controls (P< 0.0001) and 18 patients with rheumatoid arthritis (P< 0.01). In SLE patients, OAZ transcripts were positively correlated with SLE disease activity index (SLEDAI) score (r = 0.72,P< 0.0001) and higher in those positive for anti-dsDNA or anti-Sm antibodies (bothP< 0.05). Co-culturing with OAZ siRNAs reduced mRNA levels of OAZ by 74.6 ± 6.4% as compared to those co-cultured with non-targeting siRNA and OAZ silencing resulted in reduced total IgG, ANA, interferon (IFN)-γ, interleukin (IL)-10, IL-12 and IL-21, but elevated CCL2 levels in culture supernatants (P< 0.05). The declined ANA levels correlated with inhibited OAZ expression (r = 0.88,P= 0.05), reduced IL-21 levels (r = 0.99,P< 0.01), and elevated chemokine (C-C motif) ligand 2 levels (r = -0.98,P< 0.01). Expressions of ID1-3 were significantly down-regulated by 68.7%, 70.2% and 67.7% respectively after OAZ silence, while ID3 was also highly expressed in SLE PBLs (P< 0.0001) and associated with disease activity (r = 0.76,P< 0.0001) as well as anti-dsDNA or anti-Sm antibodies (bothP< 0.05).ConclusionsElevated expression of OAZ transcripts in SLE PBLs were strongly correlated with disease activity. Suppression of OAZ expression inhibited downstream ID levels, and secretion of ANA and IL-21, implicating a role of OAZ pathway in the pathogenesis of SLE.
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影响因子：
9.8
作者：
Gaffney, PM;Langefeld, CD;Behrens, TW
通讯作者：
Behrens, TW
影响因子：
5.3
作者：
Mir, Fozia;Le Breton, Guy C.
通讯作者：
Le Breton, Guy C.
影响因子：
5
作者：
Forabosco, P.;Gorman, J. D.;Criswell, L. A.
通讯作者：
Criswell, L. A.
影响因子：
20.3
作者：
Bond, HM;Mesuraca, M;Venuta, S
通讯作者：
Venuta, S
影响因子：
158.5
作者：
Hom, Geoffrey;Graham, Robert R.;Behrens, Timothy W.
通讯作者：
Behrens, Timothy W.