Molecular & Cellular Toxicology

, Volume 15, Issue 1, pp 41–48 | Cite as

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

  • Jooyeon Lee
  • Hanbyeol Lee
  • Soojin Jang
  • Seok-Ho Hong
  • Woo Jin Kim
  • Se Min Ryu
  • Sung-Min Park
  • Kyung-Hak Lee
  • Sung-Joon Cho
  • Se-Ran YangEmail author
Original Paper



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.


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


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.


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.


CMIT/MIT Pulmonary toxicity Alveolar epithelial cells Apoptosis MAPK 


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Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V. 2019

Authors and Affiliations

  • Jooyeon Lee
    • 1
  • Hanbyeol Lee
    • 1
  • Soojin Jang
    • 1
  • Seok-Ho Hong
    • 2
  • Woo Jin Kim
    • 2
  • Se Min Ryu
    • 1
  • Sung-Min Park
    • 1
  • Kyung-Hak Lee
    • 1
  • Sung-Joon Cho
    • 1
  • Se-Ran Yang
    • 1
    Email author
  1. 1.Department of Thoracic and Cardiovascular Surgery, School of MedicineKangwon National UniversityChuncheon, GangwonRepublic of Korea
  2. 2.Department of Internal Medicine, School of MedicineKangwon National UniversityChuncheon, GangwonRepublic of Korea

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