Urinary trypsin inhibitor down-regulates hyaluronic acid fragment-induced prostanoid release in cultured human amnion cells by inhibiting cyclo-oxygenase-2 expression.

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Abstract
We postulated that urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, may inhibit low molecular weight hyaluronic acid (HA) fragment-induced prostanoid release and de-novo expression of the inducible cyclo-oxygenase-2 (COX-2) isoform in human term amnion cells. Purified amnion cultures were obtained from human fetal membranes and were exposed to a HA fragment (molecular weight 35 kDa) in the presence or absence of UTI (0–5.0 μmol/l). Amnion cells treated with the HA fragment (100 nmol/l) released significantly more prostanoids (PGE2 and PGF2α) than controls (PGE2: 2.1 ± 0.13 pg/106 cells/24 h compared with 0.42 ± 0.01, P < 0.05; PGF2α: 1.0 ± 0.17 pg/106 cells/24 h compared with 0.13 ± 0.01, P < 0.05). UTI inhibited HA fragment-induced prostanoid release in a dose-dependent manner, with 50% inhibitory concentration values of 0.8 μmol/l for PGE2 and 1.9 μmol/l for PGF2α. Western blot analyses demonstrated that protein levels of COX-2 were substantially increased in amnion cells treated with HA fragment. HA fragment-mediated COX-2 production was markedly diminished by pretreatment with UTI (1.0 μmol/l). These results are the first to demonstrate that UTI is a potent inhibitor of HA fragment-induced arachidonic acid metabolism.

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