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CMIT/MIT induce apoptosis and inflammation in alveolar epithelial cells through p38/JNK/ERK1/2 signaling pathway

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Abstract

Backgrounds

The 5-chloro-2-methyl-2h-isothiazolin-3-one and 2-methyl-2h-isothiazol-3-one (CMIT/MIT) are widespread biocides that commonly found in variety of water-soluble consumer products including dentifrice, germicide and shampoo etc. Recently, in Korea, it has been reported that general population was exposed to humidifier sterilizer with CMIT/MIT as disinfectant components, and eventually more than 530 victims had been suffered severe lung disease since they had used. Although it is known to be a certain risk factor threatening public health, it is unknown to be associated with pathological cellular- and molecular-mechanisms. Therefore, in this study, we investigated the cytotoxic effect of CMIT/MIT in mouse alveolar type II epithelial cells, MLE-12 cells.

Methods

MLE-12 cells were treated with CMIT/MIT (0-50 μM) for 24 hours.

Results

In MTT assay, cellular proliferation was significantly decreased in response to CMIT/MIT treatment. In western blot analysis, protein levels of BAX/Bcl-2 and cleaved caspase-3 were significantly increased. Moreover, cell cycle-related gene were also increased. In ELISA, CMIT/MIT increased the release of pro-inflammatory cytokine of TNF-α and IL-1β. Moreover, CMIT/MIT increased the phosphorylated-ERK1/2, phosphorylated-p38, and phosphorylated-JNK1/2 protein levels in MLE-12 cells.

Conclusion

These findings suggest that CMIT/MIT exposure induce the injury of alveolar epithelial cells with inflammatory response via the p38-JNK1/2-ERK1/2 signaling pathway.

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Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea

    Jooyeon Lee, Hanbyeol Lee, Soojin Jang, Se Min Ryu, Sung-Min Park, Kyung-Hak Lee, Sung-Joon Cho & Se-Ran Yang

  2. Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea

    Seok-Ho Hong & Woo Jin Kim

Authors
  1. Jooyeon Lee
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  2. Hanbyeol Lee
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  3. Soojin Jang
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Correspondence to Se-Ran Yang.

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Lee, J., Lee, H., Jang, S. et al. CMIT/MIT induce apoptosis and inflammation in alveolar epithelial cells through p38/JNK/ERK1/2 signaling pathway. Mol. Cell. Toxicol. 15, 41–48 (2019). https://doi.org/10.1007/s13273-019-0005-0

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  • DOI: https://doi.org/10.1007/s13273-019-0005-0

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