IN-VITRO EXPRESSION OF MMP-2 AND MMP-9 IN GLIOMA-CELLS FOLLOWING EXPOSURE TO INFLAMMATORY MEDIATORS

Progression of glioma is associated with local degenerative processes which are attributed to the activity of gelatinases. As glioma cells a re candidate for secretion of these enzymes, we have studied in vitro the potential of cytokines (interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF alpha) and transforming growth factor-beta (TGF bet a(2))) to regulate the expression of gelatinase A and B (Gels A and B, respectively) in two glioma cells of human (A172) and rat origin (C6) . We showed that IL-1 and TNF alpha both induced gene expression and p rotein secretion of Gel B in both cell lines, as revealed by RT-PCR an d gelatin zymography, respectively. In C6 cells, TNF alpha had no effe ct on Gel A constitutive expression while IL-1 increased its productio n, but only at high doses. We have also demonstrated that TGF beta(2) inhibited both IL-1- or TNF alpha-induced gene expression and Gel B pr oduction in a dose-dependent manner but had no effect on Gel A secreti on. The effect of TGF beta(2) on Gel B secretion was reversed by phorb ol myristate acetate (PMA). Taken together, these data suggest that IL -1, TNF alpha and TGF beta(2) tightly regulate Gel B secretion in glio ma cells, an enzyme which is believed to play an important role in the local invasion of brain tissue by tumor cells. (C) 1998 Elsevier Scie nce B.V. All rights reserved.