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The Role of the NLRP3 Inflammasome in Fibrosis
Fibrosis leads to the deposition of collagens in organs and tissues. The resulting pathology induces a loss of function in the organ it is manifested in and this loss of function modulates the morbidity and mortality in that individual. Indeed, approximately 45% of all deaths in the Western world ca...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Open
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395884/ https://www.ncbi.nlm.nih.gov/pubmed/22802905 http://dx.doi.org/10.2174/1874312901206010080 |
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author | Artlett, Carol M |
author_facet | Artlett, Carol M |
author_sort | Artlett, Carol M |
collection | PubMed |
description | Fibrosis leads to the deposition of collagens in organs and tissues. The resulting pathology induces a loss of function in the organ it is manifested in and this loss of function modulates the morbidity and mortality in that individual. Indeed, approximately 45% of all deaths in the Western world can be attributed to fibrosis and there are no FDA approved drugs for the treatment of fibrosis. The recent discovery of the inflammasome has led to a plethora of studies investigating this inflammatory signaling pathway in a wide variety of pathogen associated diseases. Many studies have focused on the NLRP3 inflammasome and this inflammasome is activated by a wide variety of cellular alarm signals. Once activated, caspase-1 is cleaved, inducing the secretion of IL-1β and IL-18 that signal to aid in the clearance of invading organisms. However, as the knowledge of the inflammasome has expanded, it was found that it can directly control collagen synthesis, leading to the increased deposition of collagens in the tissues such as the lung, liver, heart, and skin. Mice lacking the inflammasome adaptor protein, ASC, failed to become fibrotic when exposed to bleomycin. Inhibition of caspase-1 activity in fibroblasts from patients with the fibrotic disease systemic sclerosis, decreased collagen synthesis and reduced α-smooth muscle actin expression in myofibroblasts. Taken together, these observations suggest that the inflammasome can drive the fibrotic response and paves the way for novel therapeutics to be identified. |
format | Online Article Text |
id | pubmed-3395884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Bentham Open |
record_format | MEDLINE/PubMed |
spelling | pubmed-33958842012-07-16 The Role of the NLRP3 Inflammasome in Fibrosis Artlett, Carol M Open Rheumatol J Article Fibrosis leads to the deposition of collagens in organs and tissues. The resulting pathology induces a loss of function in the organ it is manifested in and this loss of function modulates the morbidity and mortality in that individual. Indeed, approximately 45% of all deaths in the Western world can be attributed to fibrosis and there are no FDA approved drugs for the treatment of fibrosis. The recent discovery of the inflammasome has led to a plethora of studies investigating this inflammatory signaling pathway in a wide variety of pathogen associated diseases. Many studies have focused on the NLRP3 inflammasome and this inflammasome is activated by a wide variety of cellular alarm signals. Once activated, caspase-1 is cleaved, inducing the secretion of IL-1β and IL-18 that signal to aid in the clearance of invading organisms. However, as the knowledge of the inflammasome has expanded, it was found that it can directly control collagen synthesis, leading to the increased deposition of collagens in the tissues such as the lung, liver, heart, and skin. Mice lacking the inflammasome adaptor protein, ASC, failed to become fibrotic when exposed to bleomycin. Inhibition of caspase-1 activity in fibroblasts from patients with the fibrotic disease systemic sclerosis, decreased collagen synthesis and reduced α-smooth muscle actin expression in myofibroblasts. Taken together, these observations suggest that the inflammasome can drive the fibrotic response and paves the way for novel therapeutics to be identified. Bentham Open 2012-06-15 /pmc/articles/PMC3395884/ /pubmed/22802905 http://dx.doi.org/10.2174/1874312901206010080 Text en © Carol M. Artlett; Licensee Bentham Open. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Artlett, Carol M The Role of the NLRP3 Inflammasome in Fibrosis |
title | The Role of the NLRP3 Inflammasome in Fibrosis |
title_full | The Role of the NLRP3 Inflammasome in Fibrosis |
title_fullStr | The Role of the NLRP3 Inflammasome in Fibrosis |
title_full_unstemmed | The Role of the NLRP3 Inflammasome in Fibrosis |
title_short | The Role of the NLRP3 Inflammasome in Fibrosis |
title_sort | role of the nlrp3 inflammasome in fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395884/ https://www.ncbi.nlm.nih.gov/pubmed/22802905 http://dx.doi.org/10.2174/1874312901206010080 |
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