Effects of pro- and anti-inflammatory cytokines and nitric oxide donors on hyaluronic acid synthesis by synovial cells from patients with rheumatoid arthritis.
The aim of the present study was to investigate the effects of (i) the pro-inflammatory cytokines IL (interleukin)-1beta, TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and anti-inflammatory cytokines IL-4 and IL-13, and (ii) NO (nitric oxide) donors on HA (hyaluronic acid) production by synovial cells from patients with rheumatoid arthritis. Synovial cells obtained from five patients with rheumatoid arthritis were incubated for 24 h without or with IL-1beta, TNF-alpha, IFN-gamma, or with this mixture for 24 h plus IL-4 or IL-13 for the last 6 h. The same cells were also incubated for 3-24 h without or with SNP (sodium nitroprusside) or SNAP (S-nitroso-N-acetyl-DL-penicillamine). HA secretion was determined by an immunoenzymic assay based on HA-specific binding by proteoglycan isolated from bovine cartilage. IL-1beta, TNF-alpha and IFN-gamma alone or in combination stimulated HA synthesis, whereas IL-4 and IL-13 dose-dependently inhibited HA production induced by Th1 cytokines. HA production was significantly increased by the presence of 1 mM SNP after 6 and 12 h (maximal effect). HA production was significantly increased by the presence of 0.01 and 0.1 mM SNAP after 12 h of incubation, and cells treated with 1 mM SNAP showed a maximal HA production after 24 h of incubation. In conclusion, the present study provides data concerning the regulatory role of pro- and anti-inflammatory cytokines and NO donors on HA metabolism in rheumatoid synovial cells and may help in understanding the pathophysiology of rheumatoid arthritis.
Chenevier-Gobeaux
Camille
C
Department of Biochemistry, Hôpital Cochin, Assistance Publique--Hôpitaux de Paris, 27 rue du Faubourg Saint-Jacques, 75679 cedex 14, France. camille@gobeaux.net
Morin-Robinet
Séverine
S
Lemarechal
Hervé
H
Poiraudeau
Serge
S
Ekindjian
Jean-Charles O G
JC
Borderie
Didier
D
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D018793:Interleukin-13; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D015847:Interleukin-4; D007371:Interferon-gamma; D006820:Hyaluronic Acid; D010396:Penicillamine