Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9110888 | Cytokine | 2005 | 14 Pages |
Abstract
Inflammatory cytokines or soluble factors are essential in the pathogenesis of rheumatoid arthritis (RA). Leflunomide is an effective disease modifying antirheumatic drug (DMARD) in RA. The objective of the present study was to evaluate for the first time the effects of A77 1726 on cytokine (interleukin (IL)-8, IL-10, IL-11 secretion and tumor necrosis factor-α soluble receptor I (sTNFRI)) shedding in human RA fibroblast-like synoviocytes (FLS). At 100 μM, we observed an increase in IL-10 secretion, a decrease in IL-11 release and no effect on sTNFRI shedding and IL-8 secretion in IL-1β-stimulated human RA FLS. Furthermore, at this dose, our results also confirmed that A77 1726 decreased IL-6 and prostaglandin E2 (PGE2) synthesis while it increased IL-1 receptor antagonist secretion (IL-1Ra). The mitogen-activated protein kinases (MAPKs) represent an attractive target for RA because they can regulate cytokine expression. At 100 μM, the effect of A77 1726 on IL-10 and IL-11 secretion seemed to be associated with the status of p38 MAPK activation. Our results confirmed the immunoregulatory action of leflunomide in the cytokine network involved in RA pathogenesis. It could shift the balance from cytokine mediated inflammation to cytokine directed inhibition of the inflammatory process.
Keywords
NF-κBEMSAsTNFRIDHODHleflunomideDMARDsIL-1RAFCSFLSNSAIDSDMEMCOXMAPKDulbecco's modified Eagle's mediumRheumatoid arthritiselectromobility shift assayIL-1 receptor antagonistcyclooxygenaseinterleukininterleukin-11Interleukin-10disease modifying antirheumatic drugsEnzyme-linked immunosorbent assayELISANon-steroidal anti-inflammatory drugsfetal calf serumnuclear factor-κBfibroblast-like synoviocytesmitogen-activated protein kinaseprostaglandin
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Authors
Pascale Vergne-Salle, David Yannick Léger, Philippe Bertin, Richard Trèves, Jean-Louis Beneytout, Bertrand Liagre,