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

Wu W, Ichihara G, Hashimoto N, Hasegawa Y, Hayashi Y, Tada-Oikawa S, Suzuki Y, Chang J, Kato M, D'Alessandro-Gabazza CN, Gabazza EC, Ichihara S - Int J Mol Sci (2014)

Bottom Line: Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. wendyvvri@med.nagoya-u.ac.jp.

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.

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(A) TGF-β level in BALF and (B) MMP-2 relative mRNA expression level in lung tissue were determined at Day 14 after administration. Mice were exposed to ZnO nanoparticles with or without BLM treatment. The number of mice was six in the SALINE-no ZnO, seven in the SALINE-10 µg of ZnO, six in the SALINE-20 µg of ZnO, six in the BLM-no ZnO, six in the BLM-10 µg of ZnO and seven in the BLM-20 µg of ZnO group. Data are the means ± SD; * p < 0.05; compared to the vehicle control.
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ijms-16-00660-f006: (A) TGF-β level in BALF and (B) MMP-2 relative mRNA expression level in lung tissue were determined at Day 14 after administration. Mice were exposed to ZnO nanoparticles with or without BLM treatment. The number of mice was six in the SALINE-no ZnO, seven in the SALINE-10 µg of ZnO, six in the SALINE-20 µg of ZnO, six in the BLM-no ZnO, six in the BLM-10 µg of ZnO and seven in the BLM-20 µg of ZnO group. Data are the means ± SD; * p < 0.05; compared to the vehicle control.

Mentions: With regard to the biochemical changes, the level of transforming growth factor (TGF)-β in BALF and the relative mRNA expression level of matrix metalloproteinase (MMP)-2 in lung tissue were found to increase in the SALINE group after exposure to 20 µg of ZnO nanoparticles (Figure 6). However, there were no ZnO-induced changes in collagen I, collagen III, MMP-2, MMP-9, tissue inhibitor of MMPs (TIMP)-1, TIMP-2 and fibroblast specific protein (FSP)-1 mRNA levels in either the SALINE or BLM groups (Figure S2). Moreover, hydroxyproline content was analyzed in the lung samples of the BLM groups of the 14-day experiment, but no significant change was found after exposure to ZnO nanoparticles (Figure S1B).


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

Wu W, Ichihara G, Hashimoto N, Hasegawa Y, Hayashi Y, Tada-Oikawa S, Suzuki Y, Chang J, Kato M, D'Alessandro-Gabazza CN, Gabazza EC, Ichihara S - Int J Mol Sci (2014)

(A) TGF-β level in BALF and (B) MMP-2 relative mRNA expression level in lung tissue were determined at Day 14 after administration. Mice were exposed to ZnO nanoparticles with or without BLM treatment. The number of mice was six in the SALINE-no ZnO, seven in the SALINE-10 µg of ZnO, six in the SALINE-20 µg of ZnO, six in the BLM-no ZnO, six in the BLM-10 µg of ZnO and seven in the BLM-20 µg of ZnO group. Data are the means ± SD; * p < 0.05; compared to the vehicle control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307267&req=5

ijms-16-00660-f006: (A) TGF-β level in BALF and (B) MMP-2 relative mRNA expression level in lung tissue were determined at Day 14 after administration. Mice were exposed to ZnO nanoparticles with or without BLM treatment. The number of mice was six in the SALINE-no ZnO, seven in the SALINE-10 µg of ZnO, six in the SALINE-20 µg of ZnO, six in the BLM-no ZnO, six in the BLM-10 µg of ZnO and seven in the BLM-20 µg of ZnO group. Data are the means ± SD; * p < 0.05; compared to the vehicle control.
Mentions: With regard to the biochemical changes, the level of transforming growth factor (TGF)-β in BALF and the relative mRNA expression level of matrix metalloproteinase (MMP)-2 in lung tissue were found to increase in the SALINE group after exposure to 20 µg of ZnO nanoparticles (Figure 6). However, there were no ZnO-induced changes in collagen I, collagen III, MMP-2, MMP-9, tissue inhibitor of MMPs (TIMP)-1, TIMP-2 and fibroblast specific protein (FSP)-1 mRNA levels in either the SALINE or BLM groups (Figure S2). Moreover, hydroxyproline content was analyzed in the lung samples of the BLM groups of the 14-day experiment, but no significant change was found after exposure to ZnO nanoparticles (Figure S1B).

Bottom Line: Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. wendyvvri@med.nagoya-u.ac.jp.

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.

Show MeSH
Related in: MedlinePlus