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CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation
CC16 is almost exclusively expressed in non-ciliated epithelial Clara cells, and widely used as a Clara cell marker. Diesel exhaust particles (DEPs), the fine particulate matters produced by diesel engines, cause or exacerbate airway-related diseases. Our previous study documented that DEP inhibits...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386526/ https://www.ncbi.nlm.nih.gov/pubmed/34339391 http://dx.doi.org/10.18632/aging.203356 |
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author | Hu, Ting Sun, Fenglan Yu, Xinjuan Li, Qinghai Zhao, Long Hao, Wanming Han, Wei |
author_facet | Hu, Ting Sun, Fenglan Yu, Xinjuan Li, Qinghai Zhao, Long Hao, Wanming Han, Wei |
author_sort | Hu, Ting |
collection | PubMed |
description | CC16 is almost exclusively expressed in non-ciliated epithelial Clara cells, and widely used as a Clara cell marker. Diesel exhaust particles (DEPs), the fine particulate matters produced by diesel engines, cause or exacerbate airway-related diseases. Our previous study documented that DEP inhibits the CC16 expression in the immortalized mouse Clara cell line through methylation of C/EBPα promoter. However, the molecular mechanism by which DEP regulates CC16 secretion is unclear. Here, we isolated CC16 containing Clara cells (CC16(+)) from human distal lung, and found that DEP inhibited CC16 secretion from CC16(+) cells via methylation of C/EBPα and inhibition of Munc18b transcription. CC16(+) cell conditioned media containing different concentrations of CC16 was prepared and used for culture of airway epithelial cells BEAS-2B with no expression of CC16. A positive correlation was observed between CC16 level and DEP-induced autophagy activity, and a negative correlation between CC16 level and DEP-induced pro-inflammatory cytokine TNF-α, IL-6, and IL-8 level, suggesting that CC16 might mitigate DEP-induced inflammation via promoting autophagy in BEAS-2B cells. This result was further confirmed by adding recombinant CC16 to BEAS-2B cells exposed to DEP. Moreover, CC16 level was significantly increased when CC16(+) cells were cultured in BEAS-2B cell conditioned medium containing TNF-α or the normal medium supplemented with recombinant TNF-α, suggesting that TNF-α induced CC16 production and secretion from CC16(+) cells. Collectively, these data point that CC16 and TNF-α form a negative feedback loop, and this negative feedback loop between Clara cells and normal airway epithelial cells protects against DEP exposure-induced inflammation. |
format | Online Article Text |
id | pubmed-8386526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-83865262021-08-27 CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation Hu, Ting Sun, Fenglan Yu, Xinjuan Li, Qinghai Zhao, Long Hao, Wanming Han, Wei Aging (Albany NY) Research Paper CC16 is almost exclusively expressed in non-ciliated epithelial Clara cells, and widely used as a Clara cell marker. Diesel exhaust particles (DEPs), the fine particulate matters produced by diesel engines, cause or exacerbate airway-related diseases. Our previous study documented that DEP inhibits the CC16 expression in the immortalized mouse Clara cell line through methylation of C/EBPα promoter. However, the molecular mechanism by which DEP regulates CC16 secretion is unclear. Here, we isolated CC16 containing Clara cells (CC16(+)) from human distal lung, and found that DEP inhibited CC16 secretion from CC16(+) cells via methylation of C/EBPα and inhibition of Munc18b transcription. CC16(+) cell conditioned media containing different concentrations of CC16 was prepared and used for culture of airway epithelial cells BEAS-2B with no expression of CC16. A positive correlation was observed between CC16 level and DEP-induced autophagy activity, and a negative correlation between CC16 level and DEP-induced pro-inflammatory cytokine TNF-α, IL-6, and IL-8 level, suggesting that CC16 might mitigate DEP-induced inflammation via promoting autophagy in BEAS-2B cells. This result was further confirmed by adding recombinant CC16 to BEAS-2B cells exposed to DEP. Moreover, CC16 level was significantly increased when CC16(+) cells were cultured in BEAS-2B cell conditioned medium containing TNF-α or the normal medium supplemented with recombinant TNF-α, suggesting that TNF-α induced CC16 production and secretion from CC16(+) cells. Collectively, these data point that CC16 and TNF-α form a negative feedback loop, and this negative feedback loop between Clara cells and normal airway epithelial cells protects against DEP exposure-induced inflammation. Impact Journals 2021-08-02 /pmc/articles/PMC8386526/ /pubmed/34339391 http://dx.doi.org/10.18632/aging.203356 Text en Copyright: © 2021 Hu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Hu, Ting Sun, Fenglan Yu, Xinjuan Li, Qinghai Zhao, Long Hao, Wanming Han, Wei CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title | CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title_full | CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title_fullStr | CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title_full_unstemmed | CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title_short | CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
title_sort | cc16-tnf-α negative feedback loop formed between clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386526/ https://www.ncbi.nlm.nih.gov/pubmed/34339391 http://dx.doi.org/10.18632/aging.203356 |
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