Independent regulation of plasminogen activator inhibitor 2 and plasminogen activator inhibitor 1 in human synovial fibroblasts.
OBJECTIVE
To study the plasminogen activator inhibitor(s) (PAI) produced in vitro by human synovial fibroblast-like cells.


METHODS
Human synovial cell explant cultures were established using cells from nonrheumatoid donors. PAI-2 and PAI-1 antigens were measured by enzyme-linked immunosorbent assay, and messenger RNA (mRNA) levels were determined by Northern blot.


RESULTS
The synovial fibroblasts produced both PAI-2 and PAI-1. Interleukin-1 (IL-1) increased PAI-2 but decreased PAI-1 formation, both at the protein and the mRNA levels. Using cyclooxygenase inhibitors, evidence was obtained that an endogenous cyclooxygenase product(s) in the IL-1-treated cultures inhibited formation of both PAIs; exogenous prostaglandin E2 (10(-7) M) reversed the effect of cyclooxygenase inhibition. The glucocorticoid dexamethasone (10(-6) to 10(-7) M) inhibited IL-1-stimulated PAI-2 formation but reversed the suppressive effect of IL-1 on PAI-1 production.


CONCLUSIONS
PAI-2 formation and PAI-1 formation can be regulated independently in human synoviocytes, illustrating the complexity of the modulation of the net PA activity expressed by these cells.
Hamilton
J A
JA
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
Cheung
D
D
Filonzi
E L
EL
Piccoli
D S
DS
Wojta
J
J
Gallichio
M
M
McGrath
K
K
Last
K
K
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D005938:Glucocorticoids; D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D009288:Naproxen; D003907:Dexamethasone; D015232:Dinoprostone; D007213:Indomethacin