Long‐standing untreated hyperuricemia could lead to gout. Several recent studies have demonstrated a significant decrease of serum urate during acute gout attack, which is an aseptic inflammation process focusing on IL‐1β. However, how IL‐1β, by itself, alters the expression and the functional activity of urate transporters in renal tubular epithelial cells is still unclear. Herein, we revealed that IL‐1β could attenuate the mRNA and protein levels of ABCG2, a major urate efflux pump, in HK‐2 cells by real‐time PCR and Western‐blot assays. Moreover, using an ABCG2 specific inhibitor and a new sensitive and specific detection system, it was found that IL‐1β also reduced the ABCG2 transporter activities. Incubation with specific inhibitors of the NF‐κB pathway partly dampened the inhibitory effect of IL‐1β on ABCG2, indicating that IL‐1β reduced the ABCG2 expression partially through the NF‐ĸB pathway. Furthermore, the decreased expression of PDZK1 induced by IL‐1β, which is dependent on the NF‐κB pathway, could account for the imbalance between the functions and expressions of ABCG2 on this status. These findings demonstrated a new role for IL‐1β, whereby it leads to the inhibition of ABCG2 in renal tubular epithelial cells; this new role probably does not encompass its involvement in the process of renal urate excretion mediated by inflammation. Therefore, other regulation mechanisms of urate reabsorption in renal tubular epithelial cells deserve to be examined in further studies.

Aim: Cumulative evidence has revealed that tolerogenic dendritic cells (tolDC) could relieve inflammation reactions in various autoimmune diseases. This study investigated the potential therapeutic application of vasoactive intestinal peptide (VIP)-induced tolDC (VIP-DC) on arthritis using collagen-induced arthritis (CIA) mice. Methods: Bone marrow cells were differentiated into dendritic cells (DC) using granulocyte macrophage colony-stimulating factor and interleukin (IL)-4. tolDC were induced by either VIP or Bay 11-7082 in vitro. Immunophenotypes and cytokine production of VIP-DC and Bay-DC were detected by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay, respectively. Bay-DC, VIP-DC and untreated DC were ip administrated to CIA mice on day 40 when arthritis was onset. The treatment effects on arthritic and pathological changes, including synovial hyperplasia, pannus formation, inflammation and bone erosion, were assessed. Results: VIP-DC (40 ng/mL) and Bay-DC (0.5 µg/mL) had a lower level of major histocompatibility complex II, CD40 and CD86 expression, reduced γ-interferon and increased IL-4 production (P < 0.05 or 0.01), compared with untreated DC. The administration of VIP-DC and Bay-DC decreased the arthritis score clinically at the end of the therapy. Pathological assessments showed that bone erosion and inflammation were alleviated in the VIP-DC group compared with those in the untreated DC group (P < 0.05 and P < 0.01, respectively). Conclusion: VIP-DC showed reduced immunogenicity and enhanced anti-inflammatory cytokine production. Both VIP-DC and Bay-DC could ameliorate arthritis in CIA mice clinically. VIP-DC were not inferior to Bay 11-7082-induced tolDC but may exert a better preventive effect on bone destruction. K E Y W O R D S collagen-induced arthritis, rheumatoid arthritis, tolerogenic dendritic cell, vasoactive intestinal peptide