The inhibitory effects of immunosuppressive factors, dexamethasone and interleukin-4, on NF-κB-mediated protease production by oral cancer

Abstract Matrix metalloproteinase-9 (MMP-9) produced by tumor cells is known to be implicated in the invasion of squamous cell carcinoma (SCC). In the process of searching for agents to inhibit MMP-9 in cancer, immunosuppressive factors, dexamethasone (DEX) and interleukin-4 (IL-4) were found to inhibit protein production as well as gene expression of MMP-9 in tumor necrosis factor α (TNFα)-stimulated SCC cells. DEX and IL-4 could also suppress the expression of urokinase type plasminogen activator (uPA) to prevent the conversion from the proenzyme form of MMP-9 to its active form. Regarding their mechanisms to inhibit the expression of MMP-9 and uPA, DEX and IL-4 had no effect on the cell surface levels of TNFα receptors, but inhibited the activation of NF-κB and NF-κB-dependent gene expression. DEX, but not IL-4, could strongly augment the TNFα-induced expression of IκBα in SCC cells. These results suggest that DEX and IL-4 suppress not only immunological reactions, but also tumor invasion by targeting NF-κB.