RESUMO
Tissue inhibitors of metalloproteinases (TIMPs) comprise a family of secreted multifunctional proteins that consists of four members (TIMP-1 to TIMP-4). TIMPs are all major inhibitors of most matrix metalloproteinases (MMPs). They are synthesized by a variety of different cells and regulated by a number of cytokines and by growth and differentiation factors. The balance between MMPs and TIMPs plays a crucial role in the turnover of extracellular matrix in normal and pathological conditions. Here, we report that the production of TIMP-1 was upregulated in interferon (IFNgamma-treated C6 astroglioma cells and that the proximal 226 bp region of the promoter of the TIMP-1 gene is responsible for IFNgamma-induced induction in C6 astroglioma cells. The induction of TIMP-1 production by IFNgamma was virtually abolished by introducing mutations into the putative SP1-response element in the promoter, indicating that the SP1 binding site conferred responsiveness onto a heterologous promoter. Together the results suggest that the IFNgamma-induced upregulation of TIMP-1 production in C6 astroglioma cells is mediated by the SP1 binding site localized in the TIMP-1 gene promoter.