TGF-β1/SMADs signaling involved in alleviating inflammation induced by nanoparticulate titanium dioxide in BV2 cells

Abstract

There are increasing safety concerns accompanying the widespread use of nanoparticulate titanium dioxide (nano-TiO2). It has been demonstrated that nano-TiO2 can cross the blood-brain barrier and enter the brain, causing damage to the nervous system, consisting mainly of neuroinflammation and neuronal apoptosis. Several studies have linked the TGF-β1/SMADs signaling to the development of inflammatory response in various organs. However, no studies have connected the induction of microglial inflammation by nano-TiO2 to this signaling. Therefore, this study aimed to investigate the role of TGF-β1/SMADs signaling in microglia inflammatory response induced by nano-TiO2. The results showed that nano-TiO2 increased the secretions of pro-inflammatory cytokines (IL-1α, IL-6, and TNF-α) and decreased the expressions of TGF-β1 and SMAD1/2/3 proteins in BV2 cells. When TGF-β1/SMADs signaling was inhibited, the inflammatory effect induced by nano-TiO2 increased, suggesting a suppressive effect of this signaling on the inflammation. In addition, exogenous TGF-β1 upregulated the expressions of TGF-β1 and SMADs1/2/3 proteins as well as decreased the secretions of pro-inflammatory cytokines (IL-1α, IL-6, and TNF-α) compared to BV2 cells treated with only nano-TiO2. Our results suggest that nano-TiO2 may inhibit the TGF-β1/SMADs signaling by suppressing the intracellular secretion of active TGF-β1, leading to microglial activation and the induction or exacerbation of inflammatory responses.