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Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin
Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and py...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380940/ https://www.ncbi.nlm.nih.gov/pubmed/26435068 http://dx.doi.org/10.1038/cmi.2015.79 |
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author | Kim, Seul-Ki Joe, Yeonsoo Chen, Yingqing Ryu, Jinhyun Lee, Jeong-Hee Cho, Gyeong Jae Ryter, Stefan W. Chung, Hun Taeg |
author_facet | Kim, Seul-Ki Joe, Yeonsoo Chen, Yingqing Ryu, Jinhyun Lee, Jeong-Hee Cho, Gyeong Jae Ryter, Stefan W. Chung, Hun Taeg |
author_sort | Kim, Seul-Ki |
collection | PubMed |
description | Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 (NLRP3) inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β (IL-1β). In this report, we show that the CO-releasing molecule (CORM-2) can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line (THP-1) in the absence and presence of lipopolysaccharide (LPS). In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-1β, and increased the levels of IL-10, in response to LPS and adenosine 5′-triphosphate (ATP), an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA (siRNA) reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-1β production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation (250 ppm) in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent with the induction of pyrin and IL-10, and the downregulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression. |
format | Online Article Text |
id | pubmed-5380940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53809402017-05-01 Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin Kim, Seul-Ki Joe, Yeonsoo Chen, Yingqing Ryu, Jinhyun Lee, Jeong-Hee Cho, Gyeong Jae Ryter, Stefan W. Chung, Hun Taeg Cell Mol Immunol Research Article Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the downregulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 (NLRP3) inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β (IL-1β). In this report, we show that the CO-releasing molecule (CORM-2) can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line (THP-1) in the absence and presence of lipopolysaccharide (LPS). In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-1β, and increased the levels of IL-10, in response to LPS and adenosine 5′-triphosphate (ATP), an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA (siRNA) reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-1β production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation (250 ppm) in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent with the induction of pyrin and IL-10, and the downregulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression. Nature Publishing Group 2017-04 2015-10-19 /pmc/articles/PMC5380940/ /pubmed/26435068 http://dx.doi.org/10.1038/cmi.2015.79 Text en Copyright © 2015 Chinese Society of Immunology and The University of Science and Technology http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Research Article Kim, Seul-Ki Joe, Yeonsoo Chen, Yingqing Ryu, Jinhyun Lee, Jeong-Hee Cho, Gyeong Jae Ryter, Stefan W. Chung, Hun Taeg Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title | Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title_full | Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title_fullStr | Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title_full_unstemmed | Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title_short | Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
title_sort | carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380940/ https://www.ncbi.nlm.nih.gov/pubmed/26435068 http://dx.doi.org/10.1038/cmi.2015.79 |
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