DMAVin Drinking Water Activated NF-κB Signal Pathway and Increased TGF-βand IL-1βExpressions in Bladder Epithelial Cells of Rats

Abstract

Dimethylarsinic acid (DMAV) is the main product of arsenic methylation metabolism in vivo and is rat bladder carcinogen and tumor promoting agent. In this study, we measured the expressions of mRNA and proteins of NF-κB pathway members, IKKα, IKKβ, p65, and p50 in rat bladder epithelium by qRT-PCR and immunohistochemical analysis after rats received drinking water containing 100 and 200 ppmDMAVfor 10 weeks. Transforming growth factor-β(TGF-β) immunoexpression in rat bladder epithelium and urine level of IL-1βalso were determined. We found thatDMAVdramatically increased the mRNA levels of NF-κB p50 and IKKαin the bladder epithelium of rats compared to the control group. Immunohistochemical examinations showed thatDMAVincreased immunoreactivities of IKKα, IKKβ, and phospho-NF-κB p50 in the cytoplasm and phospho-NF-κB p50 and p65 in nucleus of rat urothelial cells. In addition,DMAVtreated rats exhibited significantly increased inflammatory factor TGF-βimmunoreactivity in bladder epithelium and IL-1βsecretion in urine. These data suggest thatDMAVcould activate NF-κB signal pathway and increase TGF-βand IL-1βexpressions in bladder epithelial cells of rats.