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Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD

Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utili...

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Autores principales: Tien, Chia-Ping, Chen, Chia-Hung, Lin, Wen-Yuan, Liu, Chiu-Shong, Liu, Ko-Jiunn, Hsiao, Michael, Chang, Yu-Chan, Hung, Shih-Chieh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660058/
https://www.ncbi.nlm.nih.gov/pubmed/31299012
http://dx.doi.org/10.18632/aging.102077
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author Tien, Chia-Ping
Chen, Chia-Hung
Lin, Wen-Yuan
Liu, Chiu-Shong
Liu, Ko-Jiunn
Hsiao, Michael
Chang, Yu-Chan
Hung, Shih-Chieh
author_facet Tien, Chia-Ping
Chen, Chia-Hung
Lin, Wen-Yuan
Liu, Chiu-Shong
Liu, Ko-Jiunn
Hsiao, Michael
Chang, Yu-Chan
Hung, Shih-Chieh
author_sort Tien, Chia-Ping
collection PubMed
description Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utilizing PM-treated human pulmonary fibroblasts (HPF) models, we analyzed gene expression microarray data and Ingenuity Pathway Analysis (IPA) to identify that the transcription factor sterol regulatory element-binding protein 1 (SREBP1) was the main downstream regulator of Sirtuin1 (SIRT1). Quantitative PCR and western blot results showed that SIRT1 inhibited SREBP1 and further downregulated Pirin (PIR) and Nod-like receptor protein 3 (NLRP3) inflammasome after PM exposure. Inhibitors of SIRT1, SREBP1, and PIR could reverse PM-induced inflammation. An in silico analysis revealed that PIR correlated with smoke exposure and early COPD. Immunohistochemical analysis of tissue microarrays from PM-fed mouse models was used to determine the association of PIR with PM. These data demonstrate that the SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may be associated with PM-induced adverse health issues. SIRT1 functions as a protector from PM exposure, whereas PIR acts as a predictor of PM-induced pulmonary disease. The SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may present several potential therapeutic targets for PM-related adverse health events.
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spelling pubmed-66600582019-08-05 Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD Tien, Chia-Ping Chen, Chia-Hung Lin, Wen-Yuan Liu, Chiu-Shong Liu, Ko-Jiunn Hsiao, Michael Chang, Yu-Chan Hung, Shih-Chieh Aging (Albany NY) Research Paper Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utilizing PM-treated human pulmonary fibroblasts (HPF) models, we analyzed gene expression microarray data and Ingenuity Pathway Analysis (IPA) to identify that the transcription factor sterol regulatory element-binding protein 1 (SREBP1) was the main downstream regulator of Sirtuin1 (SIRT1). Quantitative PCR and western blot results showed that SIRT1 inhibited SREBP1 and further downregulated Pirin (PIR) and Nod-like receptor protein 3 (NLRP3) inflammasome after PM exposure. Inhibitors of SIRT1, SREBP1, and PIR could reverse PM-induced inflammation. An in silico analysis revealed that PIR correlated with smoke exposure and early COPD. Immunohistochemical analysis of tissue microarrays from PM-fed mouse models was used to determine the association of PIR with PM. These data demonstrate that the SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may be associated with PM-induced adverse health issues. SIRT1 functions as a protector from PM exposure, whereas PIR acts as a predictor of PM-induced pulmonary disease. The SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may present several potential therapeutic targets for PM-related adverse health events. Impact Journals 2019-07-12 /pmc/articles/PMC6660058/ /pubmed/31299012 http://dx.doi.org/10.18632/aging.102077 Text en Copyright © 2019 Tien et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Tien, Chia-Ping
Chen, Chia-Hung
Lin, Wen-Yuan
Liu, Chiu-Shong
Liu, Ko-Jiunn
Hsiao, Michael
Chang, Yu-Chan
Hung, Shih-Chieh
Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title_full Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title_fullStr Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title_full_unstemmed Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title_short Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
title_sort ambient particulate matter attenuates sirtuin1 and augments srebp1-pir axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with copd
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660058/
https://www.ncbi.nlm.nih.gov/pubmed/31299012
http://dx.doi.org/10.18632/aging.102077
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