BAFF from bone marrow-derived mesenchymal stromal cells of rheumatoid arthritis patients improves their B-cell viability-supporting properties.

Mesenchymal stromal cells (MSCs) represent a unique cell type with anti-proliferative effects on activated T and B cells. Based on our observation of differences between rheumatoid arthritis and osteoarthritis bone marrow B cells we hypothesized that rheumatoid arthritis bone marrow MSCs may enhance B-cell survival. We aimed to compare the effect of rheumatoid arthritis and osteoarthritis bone marrow-derived MSCs (rheumatoid arthritis MSCs, osteoarthritis MSCs) on the survival of healthy donor purified B cells. Rheumatoid arthritis and osteoarthritis MSCs were isolated from patients undergoing hip replacement surgery, and cultured in vitro for 2-5 passages. Washed cells were co-cultured with CD20+ B cells for 30-90 hours. Cell survival was analysed using 7-amino-actinomycin D labelling by flow cytometry. Expression of mRNA and protein was determined by RT-PCR and flow cytomery. Co-culture with both rheumatoid arthritis MSCs and osteoarthritis MSCs significantly enhanced B-cell survival, the effect being more prominent in rheumatoid arthritis MSCs. Both types of MSCs displayed expression of B cell-activating factor mRNA and protein. Blocking B cell-activating factor signalling from MSCs by specific anti-B cell-activating factor and anti-B cell-activating factor receptor antibodies weakly reversed the effect of MSCs on B-cell survival mainly in rheumatoid arthritis MSCs. MSC interaction with B cells provides stimuli for B-cell survival and therefore may contribute to the pathogenesis of rheumatoid arthritis. MSC-derived factors other than B cell-activating factor are likely to contribute to this effect. This feature is more prominent in rheumatoid arthritis MSCs, possibly due to the B cell-activating factor.

Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytes.

Fibroblast-like synoviocytes (FLS) participate in rheumatoid arthritis (RA) chronic synovitis by producing pro-inflammatory cytokines (IL-6, IL-8), growth factors (VEGF) and other inflammatory mediators (PGE2, NO). We have previously reported that Tau-Cl, generated by neutrophils, inhibits in vitro some of these pathogenic RA FLS functions. Taurine bromamine (Tau-Br) originates from eosinophils and neutrophils, and its immunoregulatory activities are poorly known. Therefore, we investigated the effects of Tau-Br on RA FLS functions and compared it to Tau-Cl anti-inflammatory action. When applied at noncytotoxic concentrations: (i) Tau-Br inhibited IL-6 and PGE2 production with potency similar to Tau-Cl (IC50 approximately 250 microM), (ii) Tau-Br failed to affect VEGF and IL-8 synthesis, while Tau-Cl exerted inhibitory effect (IC50 approximately 400 microM), (iii) none of these compounds affected NO generation and iNOS expression. Thus, Tau-Cl is more effective than Tau-Br in normalization of pro-inflammatory RA FLS functions.

Taurine chloramine inhibits proliferation of rheumatoid arthritis synoviocytes by triggering a p53-dependent pathway.

OBJECTIVE AND DESIGN: Taurine chloramine (Tau-Cl), originating from activated neutrophils, possesses antiinflammatory activities. Fibroblast-like synoviocytes (FLS) participate in the chronic synovitis and synovial membrane hyperplasia that are characteristic pathological features of rheumatoid arthritis (RA). The present study was conducted to investigate the mechanism of the Tau-Cl effect on the proliferation of these cells in culture. MATERIALS AND METHODS: FLS were stimulated in vitro with platelet derived growth factor (PDGF) alone or together with Tau-Cl. Cell proliferation was evaluated by counting the total and dividing cell numbers and by measurement of (3)H-thymidine incorporation. Expression of the key cell-cycle regulators was evaluated at the protein (Western blotting) and/or mRNA (RT-PCR) levels. RESULTS: Treatment of RA FLS with Tau-Cl (200-500 microM) resulted in an early nuclear accumulation of p53 tumor suppressor protein. Moreover, Tau-Cl inhibited PDGF-triggered cell proliferation (IC(50) value approximately 250-300 microM), accompanied by characteristic modulation of p53 transcriptional targets: down-regulation of proliferating cell nuclear antigen (PCNA) and survivin, and concomitant up-regulation of p21 mitotic inhibitor. CONCLUSION: We propose that Tau-Cl inhibits proliferation of RA FLS by triggering a p53-dependent cell-cycle arrest and conclude that this compound suppresses pathways in FLS that are known to contribute to the pathology of RA.

The effect of taurine chloramine on pro-inflammatory cytokine production by peripheral blood mononuclear cells isolated from rheumatoid arthritis and osteoarthritis patients.

OBJECTIVE: Pro-inflammatory cytokines play a critical role in the pathogenesis of RA. A natural oxidant, TauCl exerts anti-inflammatory activities. Here, the effects of Tau and TauCl on key pro-inflammatory cytokines--IL-1beta, IL-6 and TNF-alpha production by LPS-triggered peripheral blood mononuclear cells (PBMCs) isolated from RA and OA patients and healthy blood donors--were examined. METHODS: PBMCs were stimulated with LPS (24 h) in the presence of Tau or TauCl (200-400 microM). Cytokine production was measured in culture supernatants (secreted) and cells lysates (cell-associated) using specific ELISAs. RESULTS: Production of the secretedforms of IL-1beta and IL-6 was inhibited by TauCl with IC50 approximately equal to 250 microM and 300-400 microM respectively, in all investigated groups. In all cultures of PBMCs TauCl raised the TNF-alpha production at the low concentration (200 mM), while at the higher concentration (400 microM) either reduced it (55% of RA, 70% of OA patients and 55% of healthy donors) or exerted no effect (remainder of patients). Interestingly, Tau did not significantly affect any cytokine production. CONCLUSION: TauCl at high concentrations down-regulates pro-inflammatory cytokine production. However, the impact of TauCl on TNF-alpha production by PBMCs from RA is more limited than in cells isolated from OA patients.