Prostaglandin E2 receptors,EP2 and EP4, regulate expression of surface molecules and cytokines in B-cells of collagen-induced arthritic mice

AIM: To observe the immunoregulatory effects of prostaglandin E₂ receptor (EP) subtypes EP2/EP4 on the B-cells of collagen-induced arthritic(CIA)mice. METHODS: DBA/1 mice were immunized with chicken type II collagen emulsified in Freunds complete adjuvant to induce arthritis. B-cells were isolated from the splenocyte suspension by positive selection using anti-CD19 monoclonal antibody immunomagnetic beads. The expression of MHC II, CD 80 and CD86 was examined by flow cytometry. The mRNA levels of EPs, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-6, IL-4, IL-10 and transforming growth factor-β (TGF-β) were detected by real-time RT-PCR. RESULTS: The rank of the mRNA levels of EPs was EP2>EP1>EP3>EP4 in B-cells and EP2/EP4 mRNA expression was obviously increased in CIA mice. EP2 antagonists inhibited the expression of MHC II, CD80 and CD86. EP4 antagonist had little effect on CD80. EP2/EP4 antagonists inhibited the mRNA expression of IFN-γ, TNF-α, and IL-6 (P<0.05 or P<0.01) and increased the expression of IL-10 (P<0.01 or P<0.05). Furthermore, the antagonists of EP2 and EP4 also increased the mRNA expression of IL-4 and TGF-β (P<0.01), respectively. CONCLUSION: PGE₂ modulate the pathogenesis of CIA via EP2/EP4 by regulating the expression of surface molecules and cytokines in B-cells. EP2/EP4 may be a new therapeutic target for treating rheumatoid arthritis.