EFFECTS OF DEXAMETHASONE AND CELL-PROLIFERATION ON THE EXPRESSION OF MATRIX METALLOPROTEINASES IN HUMAN MUCOSAL NORMAL AND MALIGNANT-CELLS

Matrix metalloproteinases (MMPs) have an important role in many biolog ical processes, such as tumor metastasis, wound healing, and inflammat ion. The regulation of MMPs and their inhibitors is still not known in detail, and the aim of this study was to investigate the effects of d examethasone on cultured oral benign and malignant cell Lines. The exp ression of MMPs in culture was studied: in four gingival (GF) and one periodontal ligament (PLF) fibroblast cell lines; in six gingival kera tinocyte (GK) cell lines; and in UNR (UNR-108, Rat Osteogenic sarcoma) and SCC (SCC-25, Human Tongue Squamous Cell Carcinoma) cell Lines. In the GFs, PLFs, and UNR cells, only MMP-2 (72 kDa gelatinase) was dete cted by gelatin zymography, while in most of the GK cell Lines only MM P-9 (92 kDa gelatinase) was observed. In confluent SCC cultures, both MMP-2 and MMP-9 were found, while only MMP-2 was seen in rapidly growi ng SCC cells, demonstrating that cell proliferation influenced gelatin ase expression in these cells, but not in the other cell lines studied . Dexamethasone at concentrations of 10(-5) mol/L and 10(-7) mol/L dec reased the production of gelatinases in the GFs and PLFs, but not in t he GKs, SCC, or UNR cells. The expression of mRNAs for matrix metallop roteinases (MMP-1 [interstitial collagenase] and MMP-2) and their inhi bitors (TLMP-1 and TLMP-2) was also studied in the GFs by Northern hyb ridization. Dexamethasone markedly decreased the amount of MMP-2 mRNA in the GFs. The mRNA level of MMP-1 decreased even more in the same GF s. The mRNA levels for TIMP-1 and TIMP-2 were also decreased by dexame thasone in the GFs. Cell proliferation influenced the degree to which dexamethasone decreased these mRNA levels. The results indicate that g lucocorticoids decrease the levels of MMPs and TIMPs in oral fibroblas tic cells, whereas they do not appear to affect the production of gela tinases in either normal or malignant oral epithelial cell lines.