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

Chem Res Toxicol. 2014 Nov 17;27(11):1934-42. doi: 10.1021/tx5002783. Epub 2014 Oct 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arsenic / toxicity*
  • Arsenic / urine
  • Cell Line
  • Cytokines / biosynthesis
  • Cytokines / urine*
  • Environmental Exposure / analysis*
  • Environmental Pollutants / toxicity*
  • Environmental Pollutants / urine
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Real-Time Polymerase Chain Reaction
  • Urothelium / cytology
  • Urothelium / drug effects*
  • Urothelium / immunology*

Substances

  • Cytokines
  • Environmental Pollutants
  • Arsenic