Tumor necrosis factor alpha (TNF alpha) induces pro-matrix metalloproteinase 9 production in human uterine cervical fibroblasts but interleukin 1 alpha antagonizes the inductive effect of TNF alpha

We have examined the regulation of precursor of matrix metalloproteinase 9 (proMMP-9)/progelatinase B production by tumor necrosis factor alpha (TNF alpha) and interleukin 1 alpha (IL-1 alpha) using human uterine cervical fibroblasts. TNF alpha, but not IL-1 alpha, induces the production of proMMP-9 in the cervical cells, IL-1 alpha, however, suppresses the TNF alpha-induced proMMP-9 production. 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulates the cervical cells to produce proMMP-9, and IL-1 alpha synergistically enhances its production. TNF alpha-induced proMMP-9 production is not mediated by protein kinase C (PKC), whereas the effect of IL-1 alpha is through PKC. By contrast, proMMP-3/prostromelysin 1 is up-regulated by TNF alpha or TPA in the presence of IL-1 alpha, whose modulation is PKC-dependent. The suppressive effect of IL-1 alpha on the TNF alpha-induced proMMP-9 production is a new biological effect of IL-1 on MMP production.