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转录因子 Blimp1 在系统性红斑狼疮中的上调。

Up-regulation of transcription factor Blimp1 in systemic lupus erythematosus.

机构信息

Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

出版信息

Mol Immunol. 2013 Dec;56(4):574-82. doi: 10.1016/j.molimm.2013.05.241. Epub 2013 Aug 1.

DOI:10.1016/j.molimm.2013.05.241
PMID:23911415
Abstract

PURPOSE

B lymphocyte induced maturation protein 1 (Blimp1) is a transcription factor that is critical for differentiation and antibody production in plasma cells. In order to understand the mechanism of systemic lupus erythematosus (SLE), the role of Blimp1 expression was studied in patients with SLE and in healthy control subjects. And Blimp1 tissue distribution in MRL/lpr lupus mice was also investigated.

METHODS

The mRNA expression level of Blimp1 was analyzed by fluorescent real time PCR and compared between the 40 SLE patients and 30 control subjects. Expression of CD138, CD27 and CD19 in peripheral blood cells was analyzed by flow cytometry. Blimp1 mRNA and protein expression levels and tissue distribution in the kidneys, spleen and lymph nodes of MRL/lpr lupus and normal mice were analyzed.

RESULTS

Blimp1 mRNA expression level was 2.1 times greater in the SLE group as compared to the control group. The increased mRNA expression of Blimp1 seemed to be related to SLE disease activity and anti-nuclear antibody (ANA) titer. In SLE patients, the CD138+ plasma cells increased as the CD27+ cells decreased. Compared with normal mice, Blimp1 was strongly expressed in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice. The expression level of Blimp1 mRNA in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice was much higher than normal mice (1.76, 2.02, and 2.05 times greater, respectively, P<0.05). Similarly, protein levels in the above mentioned organs were also much higher (1.54, 1.99, and 2.21 times greater, respectively, P<0.05).

CONCLUSIONS

The elevated expression of Blimp1 in SLE patients and in the lupus mouse model is correlated with increases in plasma cells, autoantibodies and disease activity. It is closely related to differentiation of B-lymphocytes, antibody production and renal lesions. Blimp1 may play a role in SLE disease development.

摘要

目的

B 淋巴细胞诱导成熟蛋白 1(Blimp1)是一种转录因子,对浆细胞的分化和抗体产生至关重要。为了了解系统性红斑狼疮(SLE)的发病机制,研究了 Blimp1 在 SLE 患者和健康对照者中的表达及其在 MRL/lpr 狼疮小鼠中的组织分布。

方法

通过荧光实时 PCR 分析 Blimp1 的 mRNA 表达水平,并比较 40 例 SLE 患者和 30 例对照组。通过流式细胞术分析外周血细胞中 CD138、CD27 和 CD19 的表达。分析 MRL/lpr 狼疮和正常小鼠肾脏、脾脏和淋巴结中 Blimp1 的 mRNA 和蛋白表达水平及组织分布。

结果

SLE 组 Blimp1 mRNA 表达水平较对照组高 2.1 倍。Blimp1 mRNA 表达的增加似乎与 SLE 疾病活动度和抗核抗体(ANA)滴度有关。在 SLE 患者中,随着 CD27+细胞减少,CD138+浆细胞增加。与正常小鼠相比,Blimp1 在 MRL/lpr 狼疮小鼠的肾脏、淋巴结和脾脏中表达强烈。MRL/lpr 狼疮小鼠肾脏、淋巴结和脾脏的 Blimp1 mRNA 表达水平明显高于正常小鼠(分别高 1.76、2.02 和 2.05 倍,P<0.05)。同样,上述器官的蛋白水平也明显升高(分别高 1.54、1.99 和 2.21 倍,P<0.05)。

结论

SLE 患者和狼疮小鼠模型中 Blimp1 的表达升高与浆细胞、自身抗体和疾病活动度增加有关。它与 B 淋巴细胞的分化、抗体产生和肾脏病变密切相关。Blimp1 可能在 SLE 疾病的发生发展中起作用。

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