Matache Cristiana, Stefanescu Maria, Dragomir Cristina, Tanaseanu Stefanita, Onu Adrian, Ofiteru Augustin, Szegli Geza
Department of Immunology, Cantacuzino National Institute of Research, Splaiul Independentei 103, Bucharest R-70 100, Romania.
J Autoimmun. 2003 Jun;20(4):323-31. doi: 10.1016/s0896-8411(03)00037-4.
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.
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。