The inhibitory effects of immunosuppressive factors, dexamethasone and interleukin-4, on NF-kappaB-mediated protease production by oral cancer.
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 alpha (TNFalpha)-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 TNFalpha receptors, but inhibited the activation of NF-kappaB and NF-kappaB-dependent gene expression. DEX, but not IL-4, could strongly augment the TNFalpha-induced expression of IkappaBalpha in SCC cells. These results suggest that DEX and IL-4 suppress not only immunological reactions, but also tumor invasion by targeting NF-kappaB.
Beppu
Mahiro
M
Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
Ikebe
Tetsuro
T
Shirasuna
Kanemitsu
K
D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha
D007166:Immunosuppressive Agents; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9