Abstract: 577

EFFECT OF URINARY TRYPSIN INHIBITOR DOMAIN II (HI-8) ON THE PRODUCTION OF MATRIX METALLOPROTEINASES IN HUMAN UTERINE CERVICAL FIBROBLASTS.

Takashi Sato¹ , Syuji Takeyama¹ , Hiroshi Kobayashi² , Toshihiko Terao² , Akira Ito^{1 *}
Department of Biochemistry, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan ¹
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handacho, Hamamatsu, Shizuoka 431-3192, Japan ²

Urinary trypsin inhibitor (UTI) which is known as a serine proteinase inhibitor is detectable in human amniotic fluid. We have reported that UTI suppresses the production of pro-matrix metalloproteinase (proMMP)-1/interstitial procollagenase and proMMP-3/prostromelysin 1 in human uterine cervical fibroblasts and chorionic cells and those enzymes are considered to participate in premature cervical ripening and rupture of fetal membrane. Recently, UTI domain II (HI-8) has been reported to possess a biological activity to inhibit serine proteinases. We herein investigated the effect of HI-8 on the production of proMMP-1 and proMMP-3 in human uterine cervical fibroblasts. Confluent human uterine cervical fibroblasts (HUCF) were treated with recombinant HI-8 (rHI-8) (1-10 M) and UTI (10 M) in the presence or the absence of interleukin 1 (IL-1) (10 ng/ml) for 24 h. The harvested culture medium and cytoplasmic RNA were subjected to Western blotting and Northern blotting to monitor proMMPs-1 and -3 production and gene expression, respectively. IL-1-induced production and gene expression of proMMP-1 and proMMP-3 were suppressed by UTI in HUCF. However, unlike UTI, HI-8 did not influence or slightly increased the production and gene expression of proMMP-1 and proMMP-3 in IL-1-treated HUCF. We conclude that HI-8 is not an active domain of UTI to suppress proMMPs production. We also suggest that a whole molecule of UTI may be structurally and functionally required for maintaining extracellular matrix metabolism in uterus.

    This abstract is being presented on Tuesday, August 3 at 4:15 PM at Todd 130.