Tissue plasminogen activator-induced secretion of type-1 plasminogen activator inhibitor in cultured human fibroblasts

Thrombosis Research
T M ReillyP B Timmermans

Abstract

Tissue plasminogen activator (t-PA) regulation of type-1 plasminogen activator inhibitor (PAI-1) secretion by WI-38 human fibroblasts was investigated utilizing a specific ELISA to measure PAI-1 antigen levels. Incubation of confluent fibroblasts with t-PA in serum-free medium resulted in a concentration and time-dependent increase in the secretion of PAI-1, with the maximum response (a two-fold increase) observed following a 4 hour incubation with 0.1 microM t-PA. This t-PA effect was reduced by cycloheximide, suggesting that the involvement of specific protein synthesis, and by inhibitors of t-PA's enzymatic activity, suggesting a requirement for a free catalytic site. The t-PA effect could not be attributed to endotoxin contamination. Increased levels in cell-associated PAI-1 were also detected following incubation of fibroblasts with t-PA. This previously undescribed effect, although seen at relatively high concentrations of t-PA, may have important biological implications.

References

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Oct 1, 1984·The Journal of Clinical Investigation·L A EricksonD J Loskutoff

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Citations

Jun 30, 1994·European Journal of Obstetrics, Gynecology, and Reproductive Biology·H A BremerH C Wallenburg
Dec 2, 1990·Cell Differentiation and Development : the Official Journal of the International Society of Developmental Biologists·D SeiffertD J Loskutoff
Feb 12, 2004·Insect Biochemistry and Molecular Biology·Weon-Kyoo YouKwang-Hoe Chung
May 7, 1999·Thrombosis Research·Y López-Aguirre, J A Páramo
Mar 1, 2012·British Journal of Haematology·Takayuki IwakiKazuo Umemura
Jul 12, 2002·American Journal of Physiology. Renal Physiology·Allison A Eddy

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