TAPI-1 was administered weekly to mice with skin fibrosis induced by daily BLM injections. TAPI-1 significantly suppressed BLM-induced skin thickness and the number of myofibroblasts.

TAPI caused a dose-dependent reduction in the amount of soluble 80-kD tumor necrosis factor (TNF) receptor (TNFR80) detectable in culture supernatants from activated T cells. In the presence of 200 uM TAPI, shedding of TNFR80 was inhibited by ~80%. The concentration of TAPI necessary for half-maximal inhibition of TNFR80 shedding is between 25 and 50 uM, which is comparable to the concentration required for half-maximal inhibition of TNF release (~50 uM) by these same cells. To investigate the effect of TAPI on synthesis and processing of TNF and TNFR80 by activated effector T cells in more detail, a pulse-chase labeling experiment was performed. To study TNF processing, effector T cells activated for 1 h with PMA/OKT3 were pulselabeled for 30 min with 35S-Cys/Met in the presence or absence of 200 uM TAPI, then chased with unlabeled Cys/Met. As expected, the 26-kD TNF propeptide was immunoprecipitated only from cell lysates, whereas the 17-kD secreted form of TNF was detected only in the supernatant.