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 transporte... More
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-?B 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.
