Sp1 interference prevents joint destruction of RA through inhibitory effects of gliostatin

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Gliostatin/thymidine phosphorylase (GLS/TP) has angiogenic and arthritogenic activities, and aberrant GLS production has been observed in the active synovial membranes of rheumatoid arthritis (RA) patients. The human GLS gene promoter contains at least seven consensus binding sites for the DNA binding protein Sp1. Here we examined whether Sp1 is necessary for GLS production in RA.Mithramycin is an aureolic-acid anti-neoplastic antibiotic used for treating cancer-related hypercalcaemia, leukemia and testicular cancer, which prevents Sp1 binding to its cognate site in DNA by modifying CG sequences. We also studied the effects of the Sp1 inhibitor mithramycin on GLS production in RA fibroblast-like synoviocytes.