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Pirfenidone regulates LPS mediated activation of neutrophils
Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672086/ https://www.ncbi.nlm.nih.gov/pubmed/33203891 http://dx.doi.org/10.1038/s41598-020-76271-3 |
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author | Evani, Shankar J. Karna, S. L. Rajasekhar Seshu, Janakiram Leung, Kai P. |
author_facet | Evani, Shankar J. Karna, S. L. Rajasekhar Seshu, Janakiram Leung, Kai P. |
author_sort | Evani, Shankar J. |
collection | PubMed |
description | Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils. |
format | Online Article Text |
id | pubmed-7672086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76720862020-11-18 Pirfenidone regulates LPS mediated activation of neutrophils Evani, Shankar J. Karna, S. L. Rajasekhar Seshu, Janakiram Leung, Kai P. Sci Rep Article Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils. Nature Publishing Group UK 2020-11-17 /pmc/articles/PMC7672086/ /pubmed/33203891 http://dx.doi.org/10.1038/s41598-020-76271-3 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Evani, Shankar J. Karna, S. L. Rajasekhar Seshu, Janakiram Leung, Kai P. Pirfenidone regulates LPS mediated activation of neutrophils |
title | Pirfenidone regulates LPS mediated activation of neutrophils |
title_full | Pirfenidone regulates LPS mediated activation of neutrophils |
title_fullStr | Pirfenidone regulates LPS mediated activation of neutrophils |
title_full_unstemmed | Pirfenidone regulates LPS mediated activation of neutrophils |
title_short | Pirfenidone regulates LPS mediated activation of neutrophils |
title_sort | pirfenidone regulates lps mediated activation of neutrophils |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672086/ https://www.ncbi.nlm.nih.gov/pubmed/33203891 http://dx.doi.org/10.1038/s41598-020-76271-3 |
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