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类风湿关节炎(RA)和多关节型幼年特发性关节炎(JRA)滑膜中核因子κB p65亚基、Fas抗原、Fas配体及Bcl-2相关蛋白的分析

Analysis of the NF-kappa B p65 subunit, Fas antigen, Fas ligand and Bcl-2-related proteins in the synovium of RA and polyarticular JRA.

作者信息

Sioud M, Mellbye O, Førre O

机构信息

Institute of Immunology and Rheumatology, National Hospital, Oslo, Norway.

出版信息

Clin Exp Rheumatol. 1998 Mar-Apr;16(2):125-34.

PMID:9536387
Abstract

OBJECTIVE

To investigate the nuclear localization of the transcription factor NF-kappa B, the status of apoptosis and the expression of the Fas antigen, Fas ligand, Bcl-2, Bcl-xL and Bax by synovial cells.

METHODS

Electrophoresis mobility shift assay (EMSA), immunohistochemical staining, two colour-flow cytometry and the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP nick end labelling (TUNEL)-technique were used.

RESULTS

The NF-kappa B p65 subunit appears to be present in the nuclei of synovial tissue and fluid cells as detected by EMSA and immunohistochemical staining. Fas antigen and Fas ligand (L) are expressed on up to 90% and 11% of CD3+ synovial fluid (SF) cells, respectively. Both the Fas antigen and its ligand are also expressed by synovial tissue cells. Interestingly, freshly isolated SF T cells upregulated the expression of Bcl-xL as compared to Bcl-2. An overexpression of Bax compared to Bcl-xL was seen in the synovial tissues (ST) of patients with ongoing apoptosis, but not in patients with few apoptotic cells.

CONCLUSIONS

NF-kappa B appear to be activated in vivo, both Fas and its ligand being expressed by synovial cells. Apoptosis is ongoing in the ST with significant patient variations. Such variations could be in part due to the level of Bax expression. Finally, the upregulation of Bcl-xL expression may contribute to the accumulation of SF infiltrating T cells.

摘要

目的

研究转录因子NF-κB的核定位、滑膜细胞的凋亡状态以及Fas抗原、Fas配体、Bcl-2、Bcl-xL和Bax的表达情况。

方法

采用电泳迁移率变动分析(EMSA)、免疫组织化学染色、双色流式细胞术以及末端脱氧核苷酸转移酶(TDT)介导的dUTP缺口末端标记(TUNEL)技术。

结果

通过EMSA和免疫组织化学染色检测发现,NF-κB p65亚基似乎存在于滑膜组织和滑膜液细胞的细胞核中。Fas抗原和Fas配体分别在高达90%和11%的CD3+滑膜液(SF)细胞上表达。Fas抗原及其配体也在滑膜组织细胞中表达。有趣的是,与Bcl-2相比,新鲜分离的SF T细胞上调了Bcl-xL的表达。在有持续凋亡的患者的滑膜组织(ST)中,与Bcl-xL相比,Bax出现过表达,但在凋亡细胞较少的患者中未出现。

结论

NF-κB似乎在体内被激活,Fas及其配体均由滑膜细胞表达。ST中存在持续的凋亡,且患者之间存在显著差异。这种差异可能部分归因于Bax的表达水平。最后,Bcl-xL表达的上调可能有助于SF浸润T细胞的积累。

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