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Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase

Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1(-/-)) to investigate the role of leukocyte-produced reactive oxygen species (...

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Autores principales: Chao, Wen-Cheng, Yen, Chia-Liang, Hsieh, Cheng-Yuan, Huang, Ya-Fang, Tseng, Yau-Lin, Nigrovic, Peter Andrija, Shieh, Chi-Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724816/
https://www.ncbi.nlm.nih.gov/pubmed/29228045
http://dx.doi.org/10.1371/journal.pone.0189453
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author Chao, Wen-Cheng
Yen, Chia-Liang
Hsieh, Cheng-Yuan
Huang, Ya-Fang
Tseng, Yau-Lin
Nigrovic, Peter Andrija
Shieh, Chi-Chang
author_facet Chao, Wen-Cheng
Yen, Chia-Liang
Hsieh, Cheng-Yuan
Huang, Ya-Fang
Tseng, Yau-Lin
Nigrovic, Peter Andrija
Shieh, Chi-Chang
author_sort Chao, Wen-Cheng
collection PubMed
description Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1(-/-)) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1(-/-) mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1(-/-) mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.
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spelling pubmed-57248162017-12-15 Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase Chao, Wen-Cheng Yen, Chia-Liang Hsieh, Cheng-Yuan Huang, Ya-Fang Tseng, Yau-Lin Nigrovic, Peter Andrija Shieh, Chi-Chang PLoS One Research Article Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1(-/-)) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1(-/-) mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1(-/-) mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung. Public Library of Science 2017-12-11 /pmc/articles/PMC5724816/ /pubmed/29228045 http://dx.doi.org/10.1371/journal.pone.0189453 Text en © 2017 Chao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chao, Wen-Cheng
Yen, Chia-Liang
Hsieh, Cheng-Yuan
Huang, Ya-Fang
Tseng, Yau-Lin
Nigrovic, Peter Andrija
Shieh, Chi-Chang
Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title_full Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title_fullStr Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title_full_unstemmed Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title_short Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
title_sort mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte nadph oxidase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724816/
https://www.ncbi.nlm.nih.gov/pubmed/29228045
http://dx.doi.org/10.1371/journal.pone.0189453
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