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Human pancreatic secretory trypsin inhibitor inhibited cell-surface proteolytic activity in human fibroblasts. In the range of concentrations which caused proteinase inhibition, fibroblast proliferation was also inhibited by this reagent and by the ovine equivalent. At lower concentrations, there was some evidence for a mitogenic effect, and this was confirmed by obvious stimulation of DNA synthesis at these concentrations. Human alpha 1-proteinase inhibitor, previously demonstrated to be an inhibitor of fibroblast proliferation, was also mitogenic at concentrations lower than those which inhibited proteolytic activity and cell proliferation. Human pancreatic secretory trypsin inhibitor and epidermal growth factor apparently work through independent mechanisms, since their mitogenic effects are additive.

Effects of Human and Ovine Pancreatic Secretory Trypsin Inhibitors on the Proliferation of Normal Human Fibroblasts