Erythropoietin and interleukin-1beta modulate nitrite production in a Swiss 3T3 cell model of rheumatoid synovial fibroblasts.
Erythropoietin (EPO), a haemopoietic growth factor and a primary regulator of erythropoiesis, is widely used to treat anaemia in various chronic complications of rheumatoid arthritis (RA). Fibroblast-like cells, found in the pannus tissue of joints, are thought to contribute to the inflammatory pathology of RA. Thus for the current study we investigated the effects of recombinant human EPO (rHuEPO) on NO metabolism, using an interleukin-1beta (IL-1beta)-stimulated Swiss 3T3 fibroblast monolayer as a model for fibroblast activity in RA. The results show that, over 3 days, both alone and in combination with the pro-inflammatory cytokine IL-1beta (10 ng/ml), rHuEPO (25 micro-units/ml) induced significant production of nitrite in cell culture supernatants. This is an indicator of NO production by nitric oxide synthase (NOS), which is a well-documented mediator of metalloproteinase-mediated tissue remodelling in RA. It therefore appears that, through modulation of NOS-dependent NO production, rHuEPO may influence remodelling of connective tissue in RA, independently of its established erythropoietic role.
Baig
S
S
Department of Sport, Exercise and Biomedical Science, University of Luton, Park Square, Bedfordshire LU1 3JU, UK.
Patel
Y
Y
Coussons
P
P
Grant
R
R
D016475:3T3 Cells; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology*; D013997:Time Factors
D007375:Interleukin-1; D009573:Nitrites; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide