Tumor necrosis factor alpha (TNFalpha) induces pro-matrix metalloproteinase 9 production in human uterine cervical fibroblasts but interleukin 1alpha antagonizes the inductive effect of TNFalpha.
We have examined the regulation of precursor of matrix metalloproteinase 9 (proMMP-9)/progelatinase B production by tumor necrosis factor alpha (TNFalpha) and interleukin 1alpha (IL-1alpha) using human uterine cervical fibroblasts. TNFalpha, but not IL-1alpha, induces the production of proMMP-9 in the cervical cells. IL-alpha, however, suppresses the TNFalpha-induced proMMP-9 production. 12-0-tetradecanoylphorbol 13-acetate (TPA) also stimulates the cervical cells to produce proMMP-9, and IL-1alpha synergistically enhances its production. TNFalpha-induced proMMP-9 production is not mediated by protein kinase C (PKC), whereas the effect of IL-1alpha is through PKC. By contrast, proMMP-3/prostromelysin 1 is up-regulated by TNFalpha or TPA in the presence of IL-1alpha, whose modulation is PKC-dependent. The suppressive effect of IL-1alpha on the TNFalpha-induced proMMP-9 production is a new biological effect of IL-1 on MMP production.
Sato
T
T
Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Ito
A
A
Ogata
Y
Y
Nagase
H
H
Mori
Y
Y
D000470:Alkaloids / Q000494:pharmacology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017364:Collagenases / Q000096:biosynthesis*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000470:Alkaloids; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate