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Arthritis Rheum. 1992 Dec;35(12):1526-34.

Independent regulation of plasminogen activator inhibitor 2 and plasminogen activator inhibitor 1 in human synovial fibroblasts.

Author information

1
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.

Abstract

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.

CONCLUSION:

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.

PMID:
1472130
DOI:
10.1002/art.1780351217
[Indexed for MEDLINE]

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