Session Title: Rheumatoid Arthritis: Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: To examine the immunomodulatory effects and mechanisms of Green Tea (−)-epigallocatechin-3-gallate (EGCG) on experimental arthritis in mice, we investigated whether EGCG can afford therapeutic benefit in collagen-induced arthritis (CIA) subjected mice.
Methods: EGCG (10 mg/kg body weight) was administered by oral feeding three times per week for three weeks after booster immunization, while the control mice were administered phosphate-buffered saline (PBS). The effects of EGCG were examined by assessment of joint swelling, histological changes, and immune cell populations, and the mice were sacrificed 7 weeks after the first immunization. The level of protein obtained from spleen cells and joint homogenates was examined by Western Blotting analysis. Serum levels of anti-type II collagen specific antibodies and cytokine production were measured by ELISA.
Results: EGCG treatment ameliorated clinical symptoms and reduced histological scores in arthritic mice (7.2 ± 1.2 vs 12.4 ± 2.3, P < 0.01). The serum concentrations of type-II collagen-specific IgG2a antibodies were significantly lower in EGCG-fed mice compared to PBS-treated mice (0.105 ± 0.01vs 0.283 ± 0.25 OD units, P < 0.05). EGCG significantly suppressed T cell activation by reducing [3H]-thymidine uptake and cell division as assessed by CFSE dilution. EGCG also reduced CD4 and CD8 T cells, B cells, marginal zone B cells, T1 and T2 transitional B-cells in the draining lymph node (dLN) and spleen, suggesting that down-regulation of several immune cell populations is one of the mechanisms of EGCG action. EGCG treatment increased the frequency of CD4+ Foxp3+ regulatory T cells (6.4 ± 1.25% vs 1.94 ± 1.0, P < 0.05) and IDO expression within CD11b+ dLN cells. The increased CD11b+ DCs elicited by EGCG could induce CD4+CD25+ Tregs in an IDO dependent manner in vitro. Additionally, CD11b+ DCs in spleen cells and the joint homogenates from EGCG-fed mice exhibited significantly increased NF-E2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) compared with PBS-fed mice, alluding to the importance of anti-oxidants.
Conclusion: EGCG ameliorated experimental arthritis in mice eliciting IDO-producing DCs and the activation of the Nrf-2 anti-oxidant pathway. Our results also indicate that ECGC may be of potential therapeutic value for inhibiting cartilage destruction and increasing immunoregulatory cells in arthritic joints. It remains to be established whether EGCG is useful for the prevention and treatment of rheumatoid arthritis.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/green-tea-epigallocatechin-3-gallate-ameliorates-murine-arthritis-by-inducing-ido-producing-dendritic-cells-via-nrf2-antioxidant-pathway/