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.