The prevention of collagen breakdown in bovine nasal cartilage by TIMP, TIMP-2 and a low molecular weight synthetic inhibitor.

Interleukin-1 stimulated bovine nasal cartilage fragments were cultured in the presence and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) completely blocked the release of collagen from the cartilage but were unable to prevent the release of proteoglycan. Similarly, a low molecular weight synthetic inhibitor (BB87) inhibited collagen release in a dose dependent manner, but was unable to inhibit proteoglycan release at the same concentrations. Significantly greater concentrations of inhibitor than those required to block collagen release did, however, block proteoglycan release. These results indicate that the therapeutic use of naturally occurring or synthetic inhibitors may provide a means of modifying the destruction of connective tissue proteins occurring in the arthritides and other connective tissue pathologies.

Tissue inhibitor of metalloproteinases: serum levels during pregnancy and labor, term and preterm.

OBJECTIVE: To determine the levels in serum of tissue inhibitor of metalloproteinases (TIMP) in pregnancy and to examine the possibility of a time course in relation to parturition, both term and preterm. METHODS: Serum tissue inhibitor of metalloproteinases was measured using an enzyme-linked immunosorbent assay. A cross-sectional study was conducted in 333 women during pregnancy, labor, and the postpartum period and in 27 nonpregnant volunteers. Longitudinal data were obtained from 22 women who provided a sample at term, during labor, and in the postpartum period. RESULTS: In uncomplicated pregnancies, serum TIMP levels were low from the onset of pregnancy until 37 weeks' gestation, in comparison to levels in nonpregnant women (P < .001). During the final weeks of pregnancy, levels rose and at 37-42 weeks were similar to nonpregnant levels. The levels did not change with the onset of labor. Serum concentrations of TIMP obtained during preterm labor were elevated compared to a control group of patients at a similar gestation who subsequently delivered at term (P < .01). Serum TIMP levels were significantly higher during the postpartum period than at all other times (P < .001). CONCLUSIONS: Changes in serum TIMP levels during and after pregnancy may parallel the remodeling of the extracellular matrix that takes place throughout this period. Further work is necessary to evaluate the prognostic value of TIMP for preterm labor.

Tissue collagenase: serum levels during pregnancy and parturition.

Serum levels of tissue collagenase, matrix metalloproteinase-1, were measured in both longitudinal and cross-sectional studies, in 332 pregnant women and 27 non-pregnant volunteers. The enzyme-linked immunosorbent assay (ELISA) used is the first described to measure collagenase in serum directly, is specific, and is rapid and reproducible. Levels were determined throughout pregnancy, during term and preterm labour, and in the post-partum period. Serum tissue collagenase levels were elevated in pregnancy (P < 0.001). There was no difference between levels of serum collagenase prior to labour at term and those observed during labour. Similarly, there was no significant difference in levels obtained during preterm labour and those at a similar gestation in women who subsequently delivered at term. No significant decrease in levels had occurred by the 4th post-partum day. In view of these findings of unaltered matrix metalloproteinase-1 levels in association with labour, previous reports of raised serum collagenase activity in association with the onset of spontaneous labour, at term and preterm gestation periods, may be due to increased neutrophil collagenase activity.