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

• Published in: Arthritis and rheumatism 1992-12, Vol.35 (12), p.1526-1534
• Main Authors: Hamilton, John A., Cheung, Daisy, Filonzi, Enrico L., Piccoli, Diana S., Wojta, Johann, Gallichio, Marisa, McGrath, Katherine, Last, Karena
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Northern; Blotting, Western; Cell physiology; Cells, Cultured; Cyclooxygenase Inhibitors - pharmacology; Dexamethasone - pharmacology; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Fibroblasts - cytology; Fibroblasts - metabolism; Fibroblasts - physiology; Fundamental and applied biological sciences. Psychology; Glucocorticoids - pharmacology; Humans; Indomethacin - pharmacology; Interleukin-1 - pharmacology; Molecular and cellular biology; Naproxen - pharmacology; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen Activator Inhibitor 1 - physiology; Plasminogen Activator Inhibitor 2 - genetics; Plasminogen Activator Inhibitor 2 - metabolism; Plasminogen Activator Inhibitor 2 - physiology; RNA, Messenger - analysis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Secretion. Exocytosis; Synovial Membrane - cytology; Synovial Membrane - metabolism; Synovial Membrane - physiology
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.1780351217

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 (10−7M) reversed the effect of cyclooxygenase inhibition. The glucocorticoid dexamethasone (10−6 to 10−7M) 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.