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FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation
BACKGROUND: FIP200, a critical autophagy initiating protein, can participate in numerous cellular functions including cancer development; however, its functional role in P. aeruginosa infection of alveolar macrophages is unknown. METHODS: To investigate the role of FIP200 in host defense, we transfe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393741/ https://www.ncbi.nlm.nih.gov/pubmed/24923305 http://dx.doi.org/10.1159/000362954 |
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author | Li, Yi Gan, Chang-pei Zhang, Shuang Zhou, Xi-kun Li, Xue-feng Wei, Yu-quan Yang, Jin-liang Wu, Min |
author_facet | Li, Yi Gan, Chang-pei Zhang, Shuang Zhou, Xi-kun Li, Xue-feng Wei, Yu-quan Yang, Jin-liang Wu, Min |
author_sort | Li, Yi |
collection | PubMed |
description | BACKGROUND: FIP200, a critical autophagy initiating protein, can participate in numerous cellular functions including cancer development; however, its functional role in P. aeruginosa infection of alveolar macrophages is unknown. METHODS: To investigate the role of FIP200 in host defense, we transfected murine alveolar macrophage MH-S cells with FIP200 siRNA. Having confirmed that FIP200 knockdown inhibited PAO1-induced autophagosme formation, we sought to characterize the underlying signaling pathways by immunoblotting. Further, we used fip200 KO mice to study the effects of fip200 deficiency on HMGB1 translocation. RESULTS: We showed that Pseudomonas PAO1 strain infection facilitated autophagosome formation, whereas knockdown of FIP200 inhibited autophagosome formation and HMGB1 expression in MH-S cells. Silencing FIP200 impaired the translocation of HMGB1 to cytosol of MH-S cells and almost abolished acetylation of HMGB1 during PAO1 infection. In contrast, FIP200 overexpression facilitated the cytosol translocation of HMGB1 from nuclei and increased acetylation of HMGB1 in PAO1-infected MH-S cells. Importantly, expression and acetylation of HMGB1 were also significantly down-regulated in fip200 KO mice following PAO1 infection. CONCLUSIONS: Collectively, these findings elucidate that FIP200 may regulate expression and translocation of HMGB1 during PAO1 infection, which may indicate novel therapeutic targets to control pulmonary infection. |
format | Online Article Text |
id | pubmed-4393741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43937412015-05-20 FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation Li, Yi Gan, Chang-pei Zhang, Shuang Zhou, Xi-kun Li, Xue-feng Wei, Yu-quan Yang, Jin-liang Wu, Min Cell Physiol Biochem Article BACKGROUND: FIP200, a critical autophagy initiating protein, can participate in numerous cellular functions including cancer development; however, its functional role in P. aeruginosa infection of alveolar macrophages is unknown. METHODS: To investigate the role of FIP200 in host defense, we transfected murine alveolar macrophage MH-S cells with FIP200 siRNA. Having confirmed that FIP200 knockdown inhibited PAO1-induced autophagosme formation, we sought to characterize the underlying signaling pathways by immunoblotting. Further, we used fip200 KO mice to study the effects of fip200 deficiency on HMGB1 translocation. RESULTS: We showed that Pseudomonas PAO1 strain infection facilitated autophagosome formation, whereas knockdown of FIP200 inhibited autophagosome formation and HMGB1 expression in MH-S cells. Silencing FIP200 impaired the translocation of HMGB1 to cytosol of MH-S cells and almost abolished acetylation of HMGB1 during PAO1 infection. In contrast, FIP200 overexpression facilitated the cytosol translocation of HMGB1 from nuclei and increased acetylation of HMGB1 in PAO1-infected MH-S cells. Importantly, expression and acetylation of HMGB1 were also significantly down-regulated in fip200 KO mice following PAO1 infection. CONCLUSIONS: Collectively, these findings elucidate that FIP200 may regulate expression and translocation of HMGB1 during PAO1 infection, which may indicate novel therapeutic targets to control pulmonary infection. 2014-05-20 2014 /pmc/articles/PMC4393741/ /pubmed/24923305 http://dx.doi.org/10.1159/000362954 Text en Copyright © 2014 S. Karger AG, Basel http://creativecommons.org/licenses/by/3.0/ This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. |
spellingShingle | Article Li, Yi Gan, Chang-pei Zhang, Shuang Zhou, Xi-kun Li, Xue-feng Wei, Yu-quan Yang, Jin-liang Wu, Min FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title | FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title_full | FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title_fullStr | FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title_full_unstemmed | FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title_short | FIP200 is Involved in Murine Pseudomonas Infection by Regulating HMGB1 Intracellular Translocation |
title_sort | fip200 is involved in murine pseudomonas infection by regulating hmgb1 intracellular translocation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393741/ https://www.ncbi.nlm.nih.gov/pubmed/24923305 http://dx.doi.org/10.1159/000362954 |
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