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Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils
BACKGROUND: Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils. More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer....
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838834/ https://www.ncbi.nlm.nih.gov/pubmed/20184723 http://dx.doi.org/10.1186/1465-9921-11-24 |
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author | Güngör, Nejla Pennings, Jeroen LA Knaapen, Ad M Chiu, Roland K Peluso, Marco Godschalk, Roger WL Van Schooten, Frederik J |
author_facet | Güngör, Nejla Pennings, Jeroen LA Knaapen, Ad M Chiu, Roland K Peluso, Marco Godschalk, Roger WL Van Schooten, Frederik J |
author_sort | Güngör, Nejla |
collection | PubMed |
description | BACKGROUND: Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils. More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer. METHODS: In the present study, we used microarrays in order to obtain a global view of the transcriptional responses of the lung to LPS in mice, which mimics an acute lung inflammation. To investigate the influence of neutrophils in this process, we depleted mice from circulating neutrophils by treatment with anti-PMN antibodies prior to LPS exposure. RESULTS: A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes, such as cytokine/chemokine activity and signalling. Down regulated genes represented nonimmune processes, such as development, metabolism and transport. Notably, the number of genes and pathways that were differentially expressed, was reduced when animals were depleted from circulating neutrophils, confirming the central role of neutrophils in the inflammatory response. Furthermore, there was a significant correlation between the differentially expressed gene list and the promutagenic DNA lesion M(1)dG, suggesting that it is the extent of the immune response which drives genetic instability in the inflamed lung. Several genes that were specifically regulated by the presence of activated neutrophils could be identified and these were mostly involved in interferon signalling, oxidative stress response and cell cycle progression. The latter possibly refers to a higher rate of cell turnover in the inflamed lung with neutrophils, suggesting that the neutrophil influx is associated with a higher risk for the accumulation and fixation of mutations. CONCLUSION: Gene expression profiling identified specific genes and pathways that are related to neutrophilic inflammation and could be associated to cancer development and indicate an active role of neutrophils in mediating the LPS induced inflammatory response in the mouse lung. |
format | Text |
id | pubmed-2838834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28388342010-03-16 Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils Güngör, Nejla Pennings, Jeroen LA Knaapen, Ad M Chiu, Roland K Peluso, Marco Godschalk, Roger WL Van Schooten, Frederik J Respir Res Research BACKGROUND: Lung cancer often develops in association with chronic pulmonary inflammatory diseases with an influx of neutrophils. More detailed information on inflammatory pathways and the role of neutrophils herein is a prerequisite for understanding the mechanism of inflammation associated cancer. METHODS: In the present study, we used microarrays in order to obtain a global view of the transcriptional responses of the lung to LPS in mice, which mimics an acute lung inflammation. To investigate the influence of neutrophils in this process, we depleted mice from circulating neutrophils by treatment with anti-PMN antibodies prior to LPS exposure. RESULTS: A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes, such as cytokine/chemokine activity and signalling. Down regulated genes represented nonimmune processes, such as development, metabolism and transport. Notably, the number of genes and pathways that were differentially expressed, was reduced when animals were depleted from circulating neutrophils, confirming the central role of neutrophils in the inflammatory response. Furthermore, there was a significant correlation between the differentially expressed gene list and the promutagenic DNA lesion M(1)dG, suggesting that it is the extent of the immune response which drives genetic instability in the inflamed lung. Several genes that were specifically regulated by the presence of activated neutrophils could be identified and these were mostly involved in interferon signalling, oxidative stress response and cell cycle progression. The latter possibly refers to a higher rate of cell turnover in the inflamed lung with neutrophils, suggesting that the neutrophil influx is associated with a higher risk for the accumulation and fixation of mutations. CONCLUSION: Gene expression profiling identified specific genes and pathways that are related to neutrophilic inflammation and could be associated to cancer development and indicate an active role of neutrophils in mediating the LPS induced inflammatory response in the mouse lung. BioMed Central 2010 2010-02-25 /pmc/articles/PMC2838834/ /pubmed/20184723 http://dx.doi.org/10.1186/1465-9921-11-24 Text en Copyright ©2010 Güngör et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Güngör, Nejla Pennings, Jeroen LA Knaapen, Ad M Chiu, Roland K Peluso, Marco Godschalk, Roger WL Van Schooten, Frederik J Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title | Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title_full | Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title_fullStr | Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title_full_unstemmed | Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title_short | Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils |
title_sort | transcriptional profiling of the acute pulmonary inflammatory response induced by lps: role of neutrophils |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838834/ https://www.ncbi.nlm.nih.gov/pubmed/20184723 http://dx.doi.org/10.1186/1465-9921-11-24 |
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