Intestinal uric acid excretion contributes to serum uric acid decrease during acute gout attack.

Abstract

Spontaneous serum uric acid (SUA) decrease has been found in many patients during acute gout attacks, but its mechanism remains unclear. The spontaneous regulation of SUA during a gout attack and its possible causes were evaluated in patients with gout. The mechanism of the spontaneous SUA decrease was further studied in Caco2 cells and a monosodium urate (MSU)-induced gout model of wild-type mice and ABCG2-/- mice. The urate transport function of intestinal epithelial cells was detected by transwell culture of Caco2 cells. Expression of ATP-binding cassette super-family G member 2 (ABCG2), IL-1β and phosphoinositide 3-kinase (PI3K)/Akt was analysed using real-time PCR, western blotting, or immunofluorescence assays. SUA decreased during acute gout attacks in both the gout patients and MSU-induced gouty mice. Increased serum CRP and IL-1β levels were correlated with the SUA decrease. Intestinal uric acid excretion and expression of ABCG2 were upregulated in the mice during acute gout attacks. In the ABCG2-/- mice, intestinal uric acid excretion significantly decreased during gout attacks. In an in vitro study of a transwell culture, ABCG2 and its upstream PI3K/Akt pathway were significantly upregulated in intestinal epithelial cells. However, ABCG2 expression and its associated intestinal uric acid transport were inhibited when PI3K/Akt was blocked by a PI3K inhibitor, LY294002. Increased intestinal urate excretion resulted in spontaneous SUA downregulation during acute gout attacks. Inflammation-induced PI3K/Akt activation and ABCG2 expression in epithelial cells might contribute to the upregulation of intestinal uric acid excretion.