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The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps
BACKGROUND: Chronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846253/ https://www.ncbi.nlm.nih.gov/pubmed/29545945 http://dx.doi.org/10.1186/s13601-018-0194-y |
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author | Ma, Yue Zheng, Chunquan Shi, Le |
author_facet | Ma, Yue Zheng, Chunquan Shi, Le |
author_sort | Ma, Yue |
collection | PubMed |
description | BACKGROUND: Chronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while its role in pathogenesis of CRS has yet to be revealed. This research study was designed to investigate the relationship between the expression level and biologic role of LRRK2 in CRS. METHODS: Expression of LRRK2 mRNA and noncoding repressor of NFAT (NRON) were examined by qRT-PCR. Protein levels of LRRK2 were performed by western blot and immunohistochemistry. Nuclear factor of activated T cells (NFAT) nuclear translocation was analyzed by immunohistochemistry. Additionally, LRRK2 mRNA and NRON expression in response to specific inflammatory stimulation was measured in human nasal epithelia cells (HNECs). RESULTS: The expression of LRRK2 was increased in CRSsNP patients (p < 0.05) and positively correlated with the expression levels of CD3 and Charot-Leyden crystal. Meanwhile, the NRON expression level is much lower in CRSsNP patients compared to both the control group and CRSwNP group (p < 0.05). Marked enhanced NFAT nuclear localization was observed in CRSwNP groups compared with the CRSsNP and control group (p < 0.0001). And the over-expression of LRRK2 was significantly regulated by lipopolysaccharide (LPS) in HNECs (p < 0.05). Moreover, IL-17A can increase LRRK2 expression and suppress NRON expression in vitro and dexamethasone can rescue the NRON inhibition. CONCLUSION: LRRK2 and NRON may play different role in CRSsNP and CRSwNP. The molecular mechanisms identified here may aid in the design of novel therapeutic strategies to improve clinical outcomes. |
format | Online Article Text |
id | pubmed-5846253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58462532018-03-15 The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps Ma, Yue Zheng, Chunquan Shi, Le Clin Transl Allergy Research BACKGROUND: Chronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while its role in pathogenesis of CRS has yet to be revealed. This research study was designed to investigate the relationship between the expression level and biologic role of LRRK2 in CRS. METHODS: Expression of LRRK2 mRNA and noncoding repressor of NFAT (NRON) were examined by qRT-PCR. Protein levels of LRRK2 were performed by western blot and immunohistochemistry. Nuclear factor of activated T cells (NFAT) nuclear translocation was analyzed by immunohistochemistry. Additionally, LRRK2 mRNA and NRON expression in response to specific inflammatory stimulation was measured in human nasal epithelia cells (HNECs). RESULTS: The expression of LRRK2 was increased in CRSsNP patients (p < 0.05) and positively correlated with the expression levels of CD3 and Charot-Leyden crystal. Meanwhile, the NRON expression level is much lower in CRSsNP patients compared to both the control group and CRSwNP group (p < 0.05). Marked enhanced NFAT nuclear localization was observed in CRSwNP groups compared with the CRSsNP and control group (p < 0.0001). And the over-expression of LRRK2 was significantly regulated by lipopolysaccharide (LPS) in HNECs (p < 0.05). Moreover, IL-17A can increase LRRK2 expression and suppress NRON expression in vitro and dexamethasone can rescue the NRON inhibition. CONCLUSION: LRRK2 and NRON may play different role in CRSsNP and CRSwNP. The molecular mechanisms identified here may aid in the design of novel therapeutic strategies to improve clinical outcomes. BioMed Central 2018-03-12 /pmc/articles/PMC5846253/ /pubmed/29545945 http://dx.doi.org/10.1186/s13601-018-0194-y Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ma, Yue Zheng, Chunquan Shi, Le The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title | The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title_full | The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title_fullStr | The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title_full_unstemmed | The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title_short | The kinase LRRK2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
title_sort | kinase lrrk2 is differently expressed in chronic rhinosinusitis with and without nasal polyps |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846253/ https://www.ncbi.nlm.nih.gov/pubmed/29545945 http://dx.doi.org/10.1186/s13601-018-0194-y |
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