Effect of titanium dioxide nanoparticles (TiO₂ NPs) on the expression of mucin genes in human airway epithelial cells

Abstract

Objective: Titanium dioxide nanoparticles (TiO₂ NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO₂ 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 TiO₂ NPs have not been elucidated. This study was conducted to characterize the effect of TiO₂ 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 TiO₂ 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: TiO₂ 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 TiO₂ NPs-induced MUC5B expression. And knockdown of ERK1, ERK2 and p38 MAPK using siRNAs significantly blocked TiO₂ NPs-induced MUC5B mRNA expression. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by TiO₂ NPs, and knockdown by TLR4 siRNA significantly attenuated TiO₂ NPs-induced MUC5B mRNA expression and the TiO₂ NPs-induced phosphorylations of ERK1/2 and p38 MAPK.

Discussion and conclusions: These results demonstrate for the first time that TiO₂ NPs induce MUC5B expression via TLR4-dependent ERK1/2 and p38 MAPK signaling pathways in respiratory epithelium.

Keywords:

• MUC5B
• mitogen-activated protein kinases
• nanoparticles
• respiratory epithelium
• titanium dioxide
• toll-like receptor 4

Acknowledgements

This work was supported by the 2015 Yeungnam University Research Grant.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by 2015 Yeungnam University Research Grant [grant number 215A380168].