Clinical immunology
Expression of metalloproteinases and their inhibitors in skin lesions of systemic sclerosis (SSc) patients

Metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases – TIMPs) are implicated in variations of extracellular matrix composition. Disregulation of ECM degradation is considered to play a key role in the pathogenesis of systemic sclerosis (SSc). Influence of MMPs and TIMPs on ECM composition may result not only from regulation of their production by fibroblasts, but also their direct role in the inflammatory process.
The aim of the present study was to investigate the expression of selected MMPs and their inhibitors in skin lesions of patients with SSc. MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, TIMP-2 and TIMP-3 were evaluated, by means of immunohistochemistry, in skin biopsies from 10 patients with SSc as well as 10 age-matched healthy controls.
Expression of MMPs and TIMPs was elevated in the skin of SSc patients in comparison with healthy skin. The overexpression of MMPs and TIMPs in SSc specimens is due to the presence of MMP-1, MMP-2, MMP-9, MMP-10, TIMP-2 and TIMP-3 within inflammatory infiltrate. In addition, certain MMPs (MMP-2 and MMP-9) and TIMP-2 were present in the stromal cells. Evaluation with three-step semiquantitative scale revealed that in SSc patients TIMPs expression appeared relatively lower when compared with MMPs.
The results of this preliminary study indicate that there are local disturbances in the expression of MMPs and their inhibitors in the skin of patients with SSc. It suggests that altered expression of MMPs/TIMPs may contribute to the development of local inflammatory infiltrated and tissue fibrosis in systemic sclerosis.