Effect of titanium dioxide nanoparticles (TiO NPs) on the expression of mucin genes in human airway epithelial cells.

OBJECTIVE

Titanium dioxide nanoparticles (TiO NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO NPs have been found to induce inflammatory response in the human respiratory tract. However, the effect and mechanism underlying the induction of major airway mucins by TiO NPs have not been elucidated. This study was conducted to characterize the effect of TiO NPs, and the mechanism involved, on the expressions of airway mucins in human airway epithelial cells.

MATERIALS AND METHODS

In NCI-H292 cells and primary cultures of normal nasal epithelial cells, the effects of TiO NPs and signaling pathway for airway mucin genes were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassays and immunoblot analysis using several specific inhibitors and small interfering RNAs (siRNAs).

RESULTS

TiO NPs increased MUC5B expression and activated the phosphorylations of extracellular signal-related kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (an ERK1/2 MAPK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited TiO NPs-induced MUC5B expression. And knockdown of ERK1, ERK2 and p38 MAPK using siRNAs significantly blocked TiO NPs-induced MUC5B mRNA expression. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by TiO NPs, and knockdown by TLR4 siRNA significantly attenuated TiO NPs-induced MUC5B mRNA expression and the TiO NPs-induced phosphorylations of ERK1/2 and p38 MAPK.

DISCUSSION AND CONCLUSIONS

These results demonstrate for the first time that TiO NPs induce MUC5B expression via TLR4-dependent ERK1/2 and p38 MAPK signaling pathways in respiratory epithelium.