Inflammatory and tumorigenic effects of environmental pollutants found in particulate matter on lung epithelial cells
(2019) In Toxicology in Vitro 59. p.300-311- Abstract
Exposure to environmental pollutants is a major public health concern. This study investigated the inflammatory and tumorigenic effects of environmental pollutants (benzene, benzo[a]pyrene, cadmium, and diisononyl phthalate) on transformed A549 and H292 lung alveolar epithelial cells and non-transformed BEAS-2B lung bronchial epithelial cells. The cytotoxic effects of the pollutants were analyzed by the methyl thiazolyl tetrazolium assay. The anchorage-independent soft agar assay demonstrated that treatment with benzene, cadmium, and diisononyl phthalate for 4 weeks induced malignant transformation of BEAS-2B cells and tumorigenesis of A549 and H292 cells. mRNA expression of the inflammation-related genes tenascin-C, matrix... (More)
Exposure to environmental pollutants is a major public health concern. This study investigated the inflammatory and tumorigenic effects of environmental pollutants (benzene, benzo[a]pyrene, cadmium, and diisononyl phthalate) on transformed A549 and H292 lung alveolar epithelial cells and non-transformed BEAS-2B lung bronchial epithelial cells. The cytotoxic effects of the pollutants were analyzed by the methyl thiazolyl tetrazolium assay. The anchorage-independent soft agar assay demonstrated that treatment with benzene, cadmium, and diisononyl phthalate for 4 weeks induced malignant transformation of BEAS-2B cells and tumorigenesis of A549 and H292 cells. mRNA expression of the inflammation-related genes tenascin-C, matrix metalloproteinase (MMP)-9, and MMP-2, as well as inhibitors of MMPs (TIMP-1 and TIMP-2), was analyzed by RT-PCR. The pollutants largely upregulated expression of MMP-9 and MMP-2, but suppressed expression of their inhibitors TIMP-1 and TIMP-2. Measurement of transepithelial electrical resistance revealed that cadmium and diisononyl phthalate significantly increased cell permeability. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor of inflammatory genes, including MMP-9 and MMP-2, while signal transducer and activator of transcription (STAT) 3 is a key regulator of malignant transformation. All the pollutants activated the NF-κB promoter, while only cadmium induced activation of the STAT3 promoter in HEK293T cells. Moreover, all the pollutants increased the phospho-NF-κB level, but only cadmium and diisononyl phthalate increased the phospho-STAT3 level in A549 and BEAS-2B cells. These findings suggest that specific environmental pollutants enhance inflammation, cell permeability, and malignant transformation in lung epithelial cells by activating the oncogenic transcription factors STAT3 and NF-κB.
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- author
- Taş, İsa LU ; Zhou, Rui ; Park, So-Yeon ; Yang, Yi ; Gamage, Chathurika D B ; Son, Young-Jin ; Paik, Man-Jeong and Kim, Hangun
- publishing date
- 2019-09
- type
- Contribution to journal
- publication status
- published
- keywords
- Benzene/toxicity, Benzo(a)pyrene/toxicity, Cadmium/toxicity, Carcinogens/toxicity, Cell Line, Cell Membrane Permeability/drug effects, Cell Transformation, Neoplastic/drug effects, Environmental Pollutants/toxicity, Epithelial Cells/drug effects, Humans, Inflammation/chemically induced, Lung/cytology, NF-kappa B/metabolism, Particulate Matter/toxicity, Phthalic Acids/toxicity, STAT3 Transcription Factor/metabolism
- in
- Toxicology in Vitro
- volume
- 59
- pages
- 300 - 311
- publisher
- Elsevier
- external identifiers
-
- pmid:31154059
- scopus:85066459916
- ISSN
- 1879-3177
- DOI
- 10.1016/j.tiv.2019.05.022
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2019 Elsevier Ltd. All rights reserved.
- id
- b37eac93-63c9-4260-becf-426841bb3009
- date added to LUP
- 2022-08-25 14:32:22
- date last changed
- 2024-05-01 12:52:49
@article{b37eac93-63c9-4260-becf-426841bb3009,
abstract = {{<p>Exposure to environmental pollutants is a major public health concern. This study investigated the inflammatory and tumorigenic effects of environmental pollutants (benzene, benzo[a]pyrene, cadmium, and diisononyl phthalate) on transformed A549 and H292 lung alveolar epithelial cells and non-transformed BEAS-2B lung bronchial epithelial cells. The cytotoxic effects of the pollutants were analyzed by the methyl thiazolyl tetrazolium assay. The anchorage-independent soft agar assay demonstrated that treatment with benzene, cadmium, and diisononyl phthalate for 4 weeks induced malignant transformation of BEAS-2B cells and tumorigenesis of A549 and H292 cells. mRNA expression of the inflammation-related genes tenascin-C, matrix metalloproteinase (MMP)-9, and MMP-2, as well as inhibitors of MMPs (TIMP-1 and TIMP-2), was analyzed by RT-PCR. The pollutants largely upregulated expression of MMP-9 and MMP-2, but suppressed expression of their inhibitors TIMP-1 and TIMP-2. Measurement of transepithelial electrical resistance revealed that cadmium and diisononyl phthalate significantly increased cell permeability. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor of inflammatory genes, including MMP-9 and MMP-2, while signal transducer and activator of transcription (STAT) 3 is a key regulator of malignant transformation. All the pollutants activated the NF-κB promoter, while only cadmium induced activation of the STAT3 promoter in HEK293T cells. Moreover, all the pollutants increased the phospho-NF-κB level, but only cadmium and diisononyl phthalate increased the phospho-STAT3 level in A549 and BEAS-2B cells. These findings suggest that specific environmental pollutants enhance inflammation, cell permeability, and malignant transformation in lung epithelial cells by activating the oncogenic transcription factors STAT3 and NF-κB.</p>}},
author = {{Taş, İsa and Zhou, Rui and Park, So-Yeon and Yang, Yi and Gamage, Chathurika D B and Son, Young-Jin and Paik, Man-Jeong and Kim, Hangun}},
issn = {{1879-3177}},
keywords = {{Benzene/toxicity; Benzo(a)pyrene/toxicity; Cadmium/toxicity; Carcinogens/toxicity; Cell Line; Cell Membrane Permeability/drug effects; Cell Transformation, Neoplastic/drug effects; Environmental Pollutants/toxicity; Epithelial Cells/drug effects; Humans; Inflammation/chemically induced; Lung/cytology; NF-kappa B/metabolism; Particulate Matter/toxicity; Phthalic Acids/toxicity; STAT3 Transcription Factor/metabolism}},
language = {{eng}},
pages = {{300--311}},
publisher = {{Elsevier}},
series = {{Toxicology in Vitro}},
title = {{Inflammatory and tumorigenic effects of environmental pollutants found in particulate matter on lung epithelial cells}},
url = {{http://dx.doi.org/10.1016/j.tiv.2019.05.022}},
doi = {{10.1016/j.tiv.2019.05.022}},
volume = {{59}},
year = {{2019}},
}