Selective induction of the secretion of cathepsins B and L by cytokines in synovial fibroblast-like cells.
We have investigated the potent influence of some cytokines, tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and interferon-gamma (IFN-gamma), on the secretion of cysteine proteinases (cathepsins B and L) by cultured synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). After treatment of synovial fibroblast-like cells with cytokines, culture media were evaluated for cathepsins B and L by enzyme immunoassays, and for cathepsin B and L activities using the enzymatic substrates. Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, and specific inhibitors. Treatment of synovial fibroblast-like cells with TNF-alpha or PDGF resulted in a marked increase in cathepsin B secretion. Moreover, after prolonged PDGF treatment, the amount of secreted cathepsin B returned to the low control level. In contrast, bFGF led to increased cathepsin L secretion. IFN-gamma induced both cathepsin B and L secretion. Our results show that cytokines induce a selective secretion of cathepsins B and L by synovial fibroblast-like cells. This selective effect of cytokines on the secretion of cysteine proteinases suggests that synovial fibroblast-like cell-mediated articular degradation is a highly regulated process.
Lemaire
R
R
Department of Rheumatology, CHRU, University of Medicine, Lille, France.
Huet
G
G
Zerimech
F
F
Grard
G
G
Fontaine
C
C
Duquesnoy
B
B
Flipo
R M
RM
D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002401:Cathepsin B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003470:Culture Media; D016207:Cytokines; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D007371:Interferon-gamma; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L