Arsenic Induced Overexpression of Inflammatory Cytokines Based on the Human Urothelial Cell Model in Vitro and Urinary Secretion of Individuals Chronically Exposed to Arsenic

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.

Metabolism, toxicity and anticancer activities of arsenic compounds

“…Moreover, increased the secretion of inflammatory factors and IL-8, TNF-α, and TGF-α expression have also been observed to be induced by arsenic exposure [119]. It is well known that arsenic species in particular trivalent methylated arsenic intermediate metabolites have high binding affinity for the cysteine residues of proteins, however, arsenic has also been recognized for inhibiting the functioning of various transcriptional co regulators, proteins and enzymes [120–123].…”

“…Notably , regarding the trivalent arsenicals interaction with Zinc finger domain of the XPA (containing Zn 2+ ) at normal physiological condition, it has been found that only methylated metabolites; MMA III and DMA III (but not iAs III ) have stronger binding affinity to zinc finger proteins [119]. In fact, the studies that have shown binding of iAs III to zinc finger peptides were mostly performed using apo-Zn finger proteins [128, 131], thus, more studies are needed to evaluate that whether iAs III can also bind to Zn finger peptides or proteins (i.e., with Zn 2+ ) even under normal physiological conditions.…”

The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile

“…In particular, lung irritants in mice have been shown to trigger release of interleukin-6 by adipocytes, a cytokine that has been shown to increase metastasis of arsenic-exposed respiratory tissue. 67,68,76 Receptors of adiponectin, a cytokine produced by adipose tissue, are expressed in the lungs and play an anti-inflammatory role; however, as more fat tissue accumulates, secretion of adiponectin decreases. 77,78 Genetically modified mice unable to produce adiponectin had overall poor lung health, suggesting a link between healthy lung function and the adipocytokine.…”

“…Here, subjects FEV 1 s or FVCs were entered in the multiple linear regression equation as the dependent variable and their ages, sex, and heights were entered as the independent variables. 68 Residuals were then calculated as the difference between the subjects observed FEV 1 or FVC and that predicted for them based on the linear regression equation and their age, sex, and height. Race had little impact on results and was not included.…”

Arsenic: A Review of the Element’s Toxicity, Plant Interactions, and Potential Methods of Remediation

“…46 In the bladder, cytokines can be inflamed by the metalloid, leading to potential malignancies. 47 Bladder cancer follows mechanisms of carcinogenesis similar to those of lung cancer. 48 Evidence suggests a synergistic relationship of the toxicant with tobacco.…”