Regulation of plasminogen activator activity in arthritic joints.
The plasminogen activator (PA)/plasmin system has been implicated in the inflammation and connective tissue remodelling occurring in arthritic joints. PA activity is detected in cultures of human monocytes, synoviocytes and chondrocytes and can be regulated by a variety of cytokines found in diseased joints; PA inhibitors (PAI-1 and/or PAI-2) are also produced by these cells. We have shown that human monocytes can synthesize both urokinase-type PA (u-PA) and tissue-type PA (t-PA). One cytokine present in rheumatoid synovial fluids, granulocyte macrophage colony stimulating factor (GM-CSF), stimulates monocyte u-PA production; since this cytokine can also be produced by activated monocytes and other cell types in joints, than a "CSF network" can be produced leading to u-PA production. Another monocyte cytokine, interleukin 1, causes human synoviocytes to increase their u-PA expression, a response which can be dependent on the presence of endogenous cyclooxygenase products; this cytokine also causes human chondrocytes and cartilage tissue to produce increased u-PA and t-PA activity, i.e., under conditions during which cartilage is resorbed.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Hart
P H
PH
Leizer
T
T
Vitti
G F
GF
Campbell
I K
IK
D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D015849:Plasminogen Inactivators; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator