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系统性红斑狼疮患者外周血单个核细胞表达或分泌的基质金属蛋白酶-9及其天然抑制剂金属蛋白酶组织抑制因子-1 。

Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

作者信息

Matache Cristiana, Stefanescu Maria, Dragomir Cristina, Tanaseanu Stefanita, Onu Adrian, Ofiteru Augustin, Szegli Geza

机构信息

Department of Immunology, Cantacuzino National Institute of Research, Splaiul Independentei 103, Bucharest R-70 100, Romania.

出版信息

J Autoimmun. 2003 Jun;20(4):323-31. doi: 10.1016/s0896-8411(03)00037-4.

Abstract

Matrix metalloproteinase-9 (MMP-9) was involved in inflammation and immune system dysfunctions. Besides immunologic abnormalities, systemic lupus erythematosus (SLE) also presents chronic inflammatory components. Therefore, a role of MMP-9 in SLE pathology might be supposed. To verify this hypothesis, SLE patients and healthy donors were compared for the MMP-9 and MMP-9 mRNA levels in peripheral blood mononuclear cells (PBMCs), the spontaneous secretion of MMP-9 and TIMP-1 and the MMP-9 activity. Thus, we found that fresh PBMCs from SLE patients expressed a significantly higher activity of MMP-9 and spontaneously released higher levels of MMP-9, as compared to healthy donors, while the secreted TIMP-1 level was the same for both groups. When the patients were sub-grouped based on disease status, the most increased pro-MMP-9 activity inside the PBMCs was identified for relapse SLE sub-group. A similar observation for SLE patients with positive serum fibrinogen was found. Following culture, the PBMCs from remission SLE patients secreted significantly higher MMP-9 level, than the PBMCs from relapse SLE patients. PBMCs from relapse SLE patients secreted the highest levels of TIMP-1, although this difference was not statistically significant. Taken together, these observations suggested the multiple roles of MMP-9 and TIMP-1 in progress of inflammation and tissue damage and/or in repair, depending on clinical stages of SLE.

摘要

基质金属蛋白酶-9(MMP-9)参与炎症和免疫系统功能障碍。除了免疫异常外,系统性红斑狼疮(SLE)还存在慢性炎症成分。因此,可以推测MMP-9在SLE病理过程中发挥作用。为了验证这一假设,对SLE患者和健康供体的外周血单个核细胞(PBMCs)中的MMP-9和MMP-9 mRNA水平、MMP-9和基质金属蛋白酶组织抑制因子-1(TIMP-1)的自发分泌以及MMP-9活性进行了比较。结果发现,与健康供体相比,SLE患者新鲜PBMCs中MMP-9的活性显著更高,且自发释放的MMP-9水平也更高,而两组分泌的TIMP-1水平相同。根据疾病状态对患者进行亚组分析时,发现复发SLE亚组PBMCs中前MMP-9活性增加最为明显。血清纤维蛋白原阳性的SLE患者也有类似观察结果。培养后,缓解期SLE患者的PBMCs分泌的MMP-9水平显著高于复发期SLE患者的PBMCs。复发期SLE患者的PBMCs分泌的TIMP-1水平最高,尽管这一差异无统计学意义。综上所述,这些观察结果表明,根据SLE的临床阶段,MMP-9和TIMP-1在炎症进展、组织损伤和/或修复中发挥多种作用。

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