Interferon-alpha 2 counteracts interleukin-1 alpha-stimulated expression of urokinase-type plasminogen activator in human foreskin microvascular endothelial cells in vitro.
We investigated the effect of interferon-alpha 2 (IFN-alpha 2) on interleukin-1 alpha (IL-1 alpha)-induced up-regulation of urokinase type plasminogen activator (u-PA) expression in human foreskin microvascular endothelial cells (HFMEC) and human umbilical vein endothelial cells (HUVEC) in vitro. When IFN-alpha 2 and IL-1 alpha were added to the cells simultaneously, IFN-alpha 2 inhibited IL-1 alpha-induced up-regulation of u-PA antigen in a dose- and time-dependent fashion in HFMEC, whereas in HUVEC no effect of IFN-alpha 2 on IL-1 alpha-induced u-PA was seen. IL-1 alpha-induced up-regulation of PAI-1 antigen in HFMEC was not counteracted by IFN-alpha 2. When IFN-alpha 2 was added to HFMEC 1 or 2 h after IL-1 alpha a significant inhibition in u-PA synthesis was seen, whereas when IFN-alpha 2 was added to the cells 8 h after IL-1 alpha no effect on the induction of u-PA synthesis by IL-1 alpha was seen. IFN-alpha 2 also inhibited significantly the IL-1 alpha stimulated up-regulation of specific u-PA mRNA expression. In conclusion, our data show that IFN-alpha 2 can counteract the IL-1 alpha-induced up-regulation of u-PA in a similar way as IFN-gamma. This effect, which seems to be specific for microvascular endothelial cells, could contribute to the modulation of endothelial cell-mediated extravascular proteolysis in processes such as wound healing, neovascularisation, and endothelial cell migration.
Wojta
J
J
Department of Diagnostic Haematology, Royal Melbourne Hospital, Parkville, Australia.
Zoellner
H
H
Gallicchio
M
M
Filonzi
E L
EL
Hamilton
J A
JA
McGrath
K
K
D002478:Cells, Cultured; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010413:Penis / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*
D007370:Interferon Type I; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator