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Toxicology. 2018 Jan 15;393:185-192. doi: 10.1016/j.tox.2017.11.017. Epub 2017 Nov 22.

Changes in expression of cytokines in polyhexamethylene guanidine-induced lung fibrosis in mice: Comparison of bleomycin-induced lung fibrosis.

Author information

1
National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup-si, Jeollabuk-do, 56212, Republic of Korea.
2
National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup-si, Jeollabuk-do, 56212, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea.
3
National Center for Efficacy Evaluation of Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup-si, Jeollabuk-do, 56212, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: khleekit@gmail.com.

Abstract

Inhalation of polyhexamethylene guanidine (PHMG) causes irreversible pulmonary injury, such as pulmonary fibrosis. However, the mechanism underlying PHMG-induced lung injury is unclear. In this study, we compared the difference in time-dependent lung injury between PHMG- and bleomycin (BLM)-treated mice and determined cytokines involved in inducing lung injury by performing cytokine antibody array analysis. Mice were treated once with 1.8mg/kg BLM or 1.2mg/kg PHMG through intratracheal instillation and were sacrificed on days 7 and 28. Bronchoalveolar lavage fluid (BALF) analysis showed that the number of neutrophils was significantly higher in PHMG-treated mice than in BLM-treated mice on day 7. Histopathological analysis showed inflammatory cell infiltration and fibrosis mainly in the terminal bronchioles and alveoli in the lungs of PHMG- and BLM-treated mice. However, continuous macrophage infiltration in the alveolar space and bronchioloalveolar epithelial hyperplasia (BEH) were only observed in PHMG-treated mice. Cytokine antibody array analysis showed that 15 and eight cytokines were upregulated in PHMG- and BLM-treated mice, respectively, on day 7. On day 28, 13 and five cytokines were upregulated in PHMG and BLM-treated mice, respectively. In addition, the expressed cytokines between days 7 and 28 in BLM-treated mice were clearly different, but were similar in PHMG-treated mice. Consequently, between PHMG- and BLM-treated mice, we observed differences in the expression patterns and types of cytokines. These differences are considered to be a result of the inflammatory processes induced by both substances, which may mainly involve macrophage infiltration. Therefore, continuous induction of the inflammatory response by PHMG may play an important role in the development of pulmonary fibrosis.

KEYWORDS:

Bleomycin; Cytokine; Polyhexamethylene guanidine; Pulmonary fibrosis

PMID:
29175452
DOI:
10.1016/j.tox.2017.11.017
[Indexed for MEDLINE]

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