Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs

Wenting Wu, Gaku Ichihara, Naozumi Hashimoto, Yoshinori Hasegawa, Yasuhiko Hayashi, Saeko Tada-Oikawa, Yuka Suzuki, Jie Chang, Masashi Kato, Corina N. D’Alessandro-Gabazza, Esteban C. Gabazza, Sahoko Ichihara

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.

Original languageEnglish
Pages (from-to)660-676
Number of pages17
JournalInternational journal of molecular sciences
Volume16
Issue number1
DOIs
Publication statusPublished - Dec 30 2015

Keywords

  • Animal model
  • Bleomycin
  • Metal fume fever
  • Pulmonary fibrosis
  • Zinc oxide nanoparticles

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Wu, W., Ichihara, G., Hashimoto, N., Hasegawa, Y., Hayashi, Y., Tada-Oikawa, S., Suzuki, Y., Chang, J., Kato, M., D’Alessandro-Gabazza, C. N., Gabazza, E. C., & Ichihara, S. (2015). Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs. International journal of molecular sciences, 16(1), 660-676. https://doi.org/10.3390/ijms16010660