CXCL12 and CXCR4 as Novel Biomarkers in Uric Acid-Induced Inflammation and Patients with Gouty Arthritis

The aim of this study was to evaluate the expression of chemokine receptor CXCR4 and its ligand CXCL12 in patients with gout and uric acid-induced inflammation. A total of 40 patients with intercritical gout and 27 controls were consecutively enrolled. The serum levels of interleukin-1β (IL-1β), IL-18, CXCL12, and CXCR4 were assessed using an enzyme-linked immunosorbent assay. The gene and protein expressions for these target molecules were measured in human U937 cells incubated with monosodium urate (MSU) crystals using a real-time reverse transcription polymerase chain reaction and Western blot analysis. Patients with intercritical gout showed higher serum IL-1β, IL-18, and CXCL12 levels, but not the serum CXCR4 level, than in the controls.The serum CXCR4 level in gout patients was associated with the serum IL-18 level, uric acid level, and uric acid/creatinine ratio (r = 0.331, p = 0.037; r = 0.346, p = 0.028; and r = 0.361, p = 0.022, respectively). U937 cells treated with MSU crystals significantly induced the CXCL12 and CXCR4 mRNA and protein expression in addition to IL-1β and IL-18. In cells transfected with IL-1β siRNA or IL-18 siRNA, the CXCL12 and CXCR4 expression was downregulated compared with the non-transfected cells in MSU crystal-induced inflammation. In this study, we revealed that CXCL12 and CXCR4 were involved in the pathogenesis of uric acid-induced inflammation and gouty arthritis.