Arsenic induced overexpression of inflammatory cytokines based on the human urothelial cell model in vitro and urinary secretion of individuals chronically exposed to arsenic.

Chronic persistent inflammation could play an important role in the pathogenesis of some malignancies, and inflammation is a critical factor for bladder cancer development. In this study, we measured urine levels of transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α), and IL-8 in arsenic exposure workers and expressions of inflammatory cytokines in human urothelial cells in vivo and in vitro. We found the concentrations of IL-8, TNF-α, and TGF-α presented in urine were significantly elevated in the high urinary arsenic workers compared with the low urinary arsenic workers. Multiple regression analysis showed that the urinary IL-8 level was significantly positively associated with urinary iAs concentration after adjusting for the confounding effects of age, employed years, body mass index (BMI), smoking, alcohol, and seafood consumption in recent 3 days. Urinary TNF-α and TGF-α levels were also significantly positively associated with urinary iAs concentration, and SMI. TGF-α level was negatively associated with age after adjusting for the confounding effects. Consistent with the results in vivo, mRNA expressions of TNF-α, TGF-α, and IL-8 and protein expressions of TGF-α, TGF-β1, and IL-8 were significantly elevated in SV-HUC-1 cells after exposure to lower concentrations of arsenite for 24h as compared to the control group. These data indicated that arsenic increased the secretion of inflammatory factors and IL-8, TNF-α, and TGF-α expression may be a useful biomarker of the effect of arsenic exposure.