Expression of the matrix metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in systemic lupus erythematosus patients.

Abstract

Background: The study aimed to look at alterations in expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and their potential use as biomarkers in the pathogensis of SLE.

Methods: SLE patients (n = 41) and healthy controls (n = 50) were recruited. Quantitative RT-PCR/ELISA assays were performed for expression of MMP and TIMP mRNA in whole blood and PBMC; and corresponding serum protein levels. Intracellular levels of MMP-2 and MMP-9 proteins were analysed by flow cytometry.

Results: Based on SLEDAI scores patients were grouped into active (SLEDAI ≥ 10) and inactive cases (SLEDAI < 10). In active cases, MMP-2 expression significantly increased and TIMP-2 expression was decreased (p < 0.0001) both at serum secretion (p = 0.0003) and mRNA (p < 0.0001) levels as compared to inactive cases. MMP-9 and TIMP-1 showed significantly reduced serum secretion and mRNA expression (p < 0.0001) in active cases as compared to inactive cases. Intracellular concentration of MMP-9 was reported to be higher in neutrophils, while MMP-2 was mainly found in lymphocytes of SLE patients as compared to controls. MMP/TIMP ratio profile was altered as SLE disease progresses.

Interpretation & conclusions: Findings suggest disturbed MMP and TIMP levels have a role in the pathogenesis of SLE.