Possible roles of arachidonic acid and its metabolites in induction of tissue plasminogen activator (t-PA) production in human fibroblast, IMR-90 cells by proteose peptone.
Proteose peptone (p.peptone) had an ability to induce tissue plasminogen activator (t-PA) production by human embryonic lung fibroblast, IMR-90 cells. We previously demonstrated that the induction was closely related to the activation of phospholipase A2 in the cells stimulated by p.peptone. In this report, we describe the involvement of arachidonate metabolism in the induction. The induction was inhibited in a dose-dependent manner by 5,8,11,14-eicosatetraenoic acid (ETYA), an inhibitor of both cycloxygenase and lypoxygenase, and also by nordihydroguaiaretic acid (NDGA), which in low concentrations selectively inhibits lipoxygenase. However, indomethacin, a specific inhibitor of cycloxygenase, had no effect on the induction. 5-hydroxyeicosatetraenoic acid (5-HETE), which is an arachidonate metabolite derived from lipoxygenase pathway, had an inductive effect, but prostaglandin E1 (PGE1), which is a metabolite from cycloxygenase pathway, had no effect on t-PA production by the cells. These results suggest that arachidonate metabolism is involved in the induction of t-PA production in IMR-90 cells by p.peptone, and that arachidonate metabolite(s) from lipoxygenase pathway is responsible for the induction.
Suzuki
A
A
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Mitsuda
S
S
Higashio
K
K
Kumasaka
T
T
D000527:Alprostadil / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D002364:Caseins / Q000494:pharmacology*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D008168:Lung / Q000196:embryology; D010446:Peptide Fragments / Q000494:pharmacology*; D010461:Peptones / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
D001095:Arachidonic Acids; D002364:Caseins; D006893:Hydroxyeicosatetraenoic Acids; D010446:Peptide Fragments; D010461:Peptones; C018135:proteose-peptone; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D010959:Tissue Plasminogen Activator; D000527:Alprostadil