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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...

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Autores principales: Hu, Ting, Sun, Fenglan, Yu, Xinjuan, Li, Qinghai, Zhao, Long, Hao, Wanming, Han, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
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.
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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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