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

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

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