A critical role of the transcription factor fli-1 in murine lupus development by regulation of interleukin-6 expression.
A critical role of the transcription factor fli-1 in murine lupus development by regulation of interleukin-6 expression.
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DOI：
10.1002/art.38818
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发表时间：
2014-12
影响因子：
13.3
通讯作者：
Zhang, Xian K.
中科院分区：
文献类型：
--
作者：
Sato, Shuzo;Richard, Mara Lennard;Brandon, Danielle;Buie, Joy N. Jones;Oates, Jim C.;Gilkeson, Gary S.;Zhang, Xian K.
Fli-1 转录因子与人类患者和动物模型中系统性红斑狼疮 (SLE) 的发病机制有关。白细胞介素 6 (IL-6) 失调也与 SLE 相关。我们研究了 Fli-1 是否直接调节 IL-6 的表达。从野生型和 Fli-1 杂合 (Fli-1+/-) MRL/lpr 小鼠收集血清，并通过 ELISA 测量 IL-6 浓度。通过实时PCR测量肾脏中IL-6的表达。从野生型和 Fli-1+/- MRL/lpr 小鼠中分离 T 细胞，并用 CD3/CD28 珠刺激，并通过 ELISA 测量上清液中 IL-6 的浓度。 MS1内皮细胞用Fli-1和对照siRNA转染，并比较脂多糖(LPS)刺激后IL-6的产生。进行染色质免疫沉淀 (ChIP) 测定以确定 Fli-1 是否与 IL-6 启动子区域结合。使用 NIH 3T3 细胞系进行瞬时转染，以研究 Fli-1 是否调节 IL-6 的表达。与野生型同窝小鼠相比，Fli-1+/- MRL/lpr 小鼠血清中的 IL-6 显着降低，肾脏中 IL-6 的表达也降低。从 Fli-1+/- MRL/lpr 小鼠中分离的 T 细胞产生较少的 IL-6。抑制内皮细胞中 Fli-1 的表达会导致 IL-6 的产生减少。 ChIP 测定显示 Fli-1 与 IL-6 启动子内的三个区域直接结合。 Fli-1 以剂量依赖性方式激活 IL-6 启动子的转录。 Fli-1 直接调节 IL-6 表达，这是 Fli-1 表达减少对狼疮产生保护作用的可能机制之一。
The Fli-1 transcription factor is implicated in the pathogenesis of systemic lupus erythematosus (SLE) in both human patients and animal models. Dysregulation of interleukin 6 (IL-6) is also associated with SLE. We investigated whether Fli-1 directly regulates the expression of IL-6. Sera were collected from wild-type and Fli-1 heterozygous (Fli-1+/−) MRL/lpr mice and the concentration of IL-6 was measured by ELISA. Expression of IL-6 in the kidney was measured by real-time PCR. T cells were isolated from wild-type and Fli-1+/− MRL/lpr mice and stimulated with CD3/CD28 beads, and the concentration of IL-6 in the supernatants was measured by ELISA. MS1 endothelial cells were transfected with Fli-1 and control siRNA, and the production of IL-6 was compared after lipopolysaccharides (LPS) stimulation. A chromatin immunoprecipitation (ChIP) assay was performed to determine whether Fli-1binds to the IL-6 promoter region. Transient transfections with the NIH 3T3 cell line were performed to study if Fli-1 regulates the expression of IL-6. Fli-1+/− MRL/lpr mice had significantly decreased IL-6 in sera and reduced expression of IL-6 in kidneys compared to wild-type littermates. The T cells isolated from Fli-1+/− MRL/lpr mice produced less IL-6. Inhibiting the expression of Fli-1 in endothelial cells resulted in reduced production of IL-6. The ChIP assay revealed direct binding of Fli-1 to three regions within the IL-6 promoter. Fli-1 activated transcription from the IL-6 promoter in a dose-dependent manner. Fli-1 directly regulates IL-6 expression as one of possible mechanisms for the protective effect in lupus of decreased Fli-1 expression.
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影响因子：
64.5
作者：
Chaki M;Airik R;Ghosh AK;Giles RH;Chen R;Slaats GG;Wang H;Hurd TW;Zhou W;Cluckey A;Gee HY;Ramaswami G;Hong CJ;Hamilton BA;Cervenka I;Ganji RS;Bryja V;Arts HH;van Reeuwijk J;Oud MM;Letteboer SJ;Roepman R;Husson H;Ibraghimov-Beskrovnaya O;Yasunaga T;Walz G;Eley L;Sayer JA;Schermer B;Liebau MC;Benzing T;Le Corre S;Drummond I;Janssen S;Allen SJ;Natarajan S;O'Toole JF;Attanasio M;Saunier S;Antignac C;Koenekoop RK;Ren H;Lopez I;Nayir A;Stoetzel C;Dollfus H;Massoudi R;Gleeson JG;Andreoli SP;Doherty DG;Lindstrad A;Golzio C;Katsanis N;Pape L;Abboud EB;Al-Rajhi AA;Lewis RA;Omran H;Lee EY;Wang S;Sekiguchi JM;Saunders R;Johnson CA;Garner E;Vanselow K;Andersen JS;Shlomai J;Nurnberg G;Nurnberg P;Levy S;Smogorzewska A;Otto EA;Hildebrandt F
通讯作者：
Hildebrandt F
影响因子：
2.6
作者：
Brayer, Kathryn J.;Kulshreshtha, Sanjeev;Segal, David J.
通讯作者：
Segal, David J.
影响因子：
2.6
作者：
Asari, Sadaki;Itakura, Shin;Ferreri, Kevin;Liu, Chih-Pin;Kuroda, Yoshikazu;Kandeel, Fouad;Mullen, Yoko
通讯作者：
Mullen, Yoko
影响因子：
20.3
作者：
Corcione, A;Benvenuto, F;Uccelli, A
通讯作者：
Uccelli, A
影响因子：
4.8
作者：
Ku, MC;Howard, S;Hata, A
通讯作者：
Hata, A