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

Yeon, Lee Joo; Lee, Hanbyeol; Jang, Soojin; Hong, Seok‐Ho; Kim, Woo Jin; Ryu, Se Min; Park, Sung Min; Lee, Kyung-Hak; SungJoonCho,; Yang, Se‐Ran

doi:10.1007/s13273-019-0005-0

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…In 2019, Yang's group demonstrated that alveolar epithelial cells (MLE-12 cells) treated with a mixture of MI/MCI presented high levels of pro-apoptotic proteins such as BAX-Bcl-2 and cleaved caspase-3. Furthermore, in the same study, the authors observed that MI/MCI led to the release of pro-inflammatory cytokines such as TNF-α and IL-1β through the upregulation of the mitogen-activated protein kinases (MAPK) signaling pathway [54]. More recently, another group demonstrated that MI was capable of inducing cellular death and the activation of pro-inflammatory responses in bronchial epithelial cells (BEAS-2B cells).…”

Section: Methodsmentioning

confidence: 88%

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

et al. 2020

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The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure–activity–toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer’s health, analytical methods for the identification and determination of this type of biocides were also discussed.

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Section: Methodsmentioning

confidence: 88%

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

et al. 2020

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“…Unexpectedly, no obvious cytotoxicity of PM10 was observed until a concentration of 2 μg/mL (data not shown). CMIT has been reported to induce toxicity to the lungs by inhibiting cell proliferation via p53/p21 related cell cycle arrest and apoptosis associated with upregulation of the MAPK pathway (Lee et al 2019 ). Moreover, PHMG has been shown to induce apoptosis via various pathways such as DNA and membrane damage (Park et al 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…SG formation was not detected in HPAEpiC, A549, and BEAS-2B cells after CMIT, PHMG, or PM10 treatment ( Figure 2 , Figure S1 and Figure S2), suggesting that CMIT, PHMG, or PM10 could not induce SG formation in A549, HPAEpiC, and BEAS-2B cells. Exposure to CMIT induces cellular responses, such as apoptosis, inflammation, and oxidative stress (Lee et al 2019 ). Furthermore, PHMG has been reported to induce endoplasmic reticulum (ER) stress (Kim et al 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Polyhexamethylene guanidine phosphate, chloromethylisothiazolinone, and particulate matter are dispensable for stress granule formation in human airway epithelial cells

Cambronero-Urena

Choi

et al. 2021

Animal Cells and Systems

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Environmental risk factors are recognized as threats to public health. Stress granules (SGs) are nonmembranous assemblies of mRNAs and proteins expressed in response to various stressors to promote cell survival. In this study, SG formation was examined to confirm the effects of polyhexamethylene guanidine phosphate (PHMG), chloromethylisothiazolinone (CMIT), and particulate matter (PM10) in airway epithelial cells, A549, HPAEpiC, and BEAS-2B cells. SGs were not observed after CMIT, PHMG, and PM10 treatments, as determined by immunofluorescence microscopy. Moreover, there was no change in the phosphorylation of the translation initiation factor eIF2αfollowing treatment with PHMG, CMIT, and PM10. Taken together, our findings might help determine the biological hazards of these materials.

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“…Another in vivo study in mice reported that intratracheal instillation of PGH also causes an increase in the levels of cytokines and fibronectin [ 24 ]. Second, two in vitro studies suggest that PHMG and CMIT/MIT induce the release of pro-inflammatory cytokines in mouse macrophage cells and mouse alveolar epithelial cells, respectively [ 9 , 25 ]. In addition, a study of human alveolar epithelial cells showed that exposure to PHMG and PGH elevates the level of the epithelial–mesenchymal transition (EMT)-related protein, an indicator of fibrotic response [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of evidence from in vitro [ 9 , 10 ] and in vivo [ 11 , 12 ] studies demonstrated that exposure to PHMG, CMIT/MIT, and PGH chemicals causes apoptosis, inflammation, and reactive oxygen stress in alveolar epithelial cells and induces airway barrier injuries, thereby leading to pulmonary inflammation and lung fibrosis. In addition, matched case-control studies (i.e., hospital-based, family-based, and community-based case-control studies) reported consistent findings of significant associations between the levels of HD exposure and the risk of a fatal lung injury called HD-associated lung injury (HDLI) [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Humidifier Disinfectant Consumption and Humidifier Disinfectant-Associated Lung Injury in South Korea: A Nationwide Population-Based Study

Yoon

Kang

Jung

et al. 2021

IJERPH

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Humidifier disinfectant (HD) is a household biocidal product used in humidifier water tanks to prevent the growth of microorganisms. In 2011, a series of lung injury cases of unknown causes emerged in children and pregnant women who had used HD in Korea. This study investigated changes in the nationwide number of cases of humidifier disinfectant-associated lung injury (HDLI) in concordance with nationwide HD consumption using data covering the entire Korean population. More than 25 kinds of HD products were sold between 1994 and 2011. The number of diagnosed HDLI, assessed by S27.3 (other injuries of lungs) of the Korea National Health Insurance Service (NHIS) data, sharply increased by 2005, subsequently decreased after 2005, and almost disappeared after 2011 in concordance with the annual number of HD sales. The number of self-reported HDLIs, assessed using data from all suspected HDLI cases registered in the Korea Ministry of Environment, changed with the annual number of HD sales, with a delay pattern, potentially induced by the late awareness of lung injury diseases. The present study suggests that changes in the nationwide annual consumption of HD products were consistent with changes in the annual number of HDLI cases in Korea.

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

Cited by 18 publications

References 41 publications

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

Polyhexamethylene guanidine phosphate, chloromethylisothiazolinone, and particulate matter are dispensable for stress granule formation in human airway epithelial cells

Humidifier Disinfectant Consumption and Humidifier Disinfectant-Associated Lung Injury in South Korea: A Nationwide Population-Based Study

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