Changes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the serum of patients with autoimmune diseases: association with age and disease activity

Abstract

Matrix metalloproteinases participate in the degradation of the extracellular matrix proteins and are regulated mainly by their respective tissue inhibitors. In a variety of inflammatory connective tissue diseases, variations in the tissue content of both metalloproteinases and tissue inhibitors have been reported. The purpose of this study was to determine the serum levels of metalloproteinases and tissue inhibitors in patients with autoimmune diseases and compare with those of healthy individuals of similar age. The metalloproteinase content was analyzed by zymography and it was found that the serum levels of metalloproteinase-2 and metalloproteinase-9 of all autoimmune disease samples were decreased, in all diseases examined and independently of clinical activity, while those of active metalloproteinase-9 were significantly elevated. Both tissue inhibitors were quantitated by direct enzyme-linked immunosorbent assay and were also found decreased in autoimmune disease samples, confirming the balance that should exist in the secretion of metalloproteinases and tissue inhibitors. These results suggested that the increased active form of metalloproteinase-9, together with the decreased concentration of tissue inhibitor-2, could be used for diagnostic purposes and for the follow-up of patients with autoimmune diseases.

Age- and Gender-Dependent Changes in Connective Tissue Remodeling: Physiological Differences in Circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 Level

“…Accelerated matrix breakdown caused by the increased activity of MMPs and/or the quantitative imbalance between MMPs and their tissue inhibitors have been implicated in several pathological conditions, including rheumatoid arthritis, tumor metastasis and heart failure [10][11][12][13] . Increased activity of circulating stromelysins, especially MMP-3, has been found in patients with systemic connective tissue diseases, including rheumatoid arthritis, scleroderma and systemic lupus erythematosus [14][15][16] . In rheumatoid arthritis, the serum MMP-3 level is regarded as a reflection of local synthesis and as such is successfully used as marker of disease activity and/or joint destruction [10,16] .…”

Tissue inhibitor of metalloproteinase-2 inhibits T-cell infiltration and preserves pancreatic β-cell function in an in vitro type 1 diabetes mellitus model

“…Recently, MMP-9 knockout mice were found to be equally sensitive to low-dose streptozotocininduced diabetes as wild type mice, suggesting that inhibition of this metalloproteinase does not play a significant role in immune-mediated diabetes [22]. Alternatively, ample work has demonstrated the intimate role that MMPs play in various aspects of tissue invasion [23] and that TIMP/MMP activity has been correlated with autoimmune disease prognosis [24].…”