Constitutive production of procollagenase and tissue inhibitor of metalloproteinases by human keratinocytes in culture.

Production of procollagenase and tissue inhibitor of metalloproteinases was demonstrated in human keratinocyte cultures. The two proteins were immunoprecipitated from keratinocyte-conditioned medium with antibodies to human dermal fibroblast collagenase and tissue inhibitor of metalloproteinases and quantitated with enzyme-linked immunosorbent assays. Treatment of the keratinocytes with the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate, produced a six to 34-fold increase in procollagenase synthesis and secretion but only a threefold increase in the production of tissue inhibitor of metalloproteinases. Collagenase and tissue inhibitor of metalloproteinases mRNAs were present in normal keratinocytes, were the same size as their fibroblast counterparts, and both increased in response to treatment with 12-0-tetradecanoylphorbol-13-acetate. These data suggest that remodeling of type I collagen may be an important function of human keratinocytes in vivo.