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Pyrin-only protein 2 limits inflammation but improves protection against bacteria

Pyrin domain-only proteins (POPs) are recently evolved, primate-specific proteins demonstrated in vitro as negative regulators of inflammatory responses. However, their in vivo function is not understood. Of the four known POPs, only POP2 is reported to regulate NF-κB-dependent transcription and mul...

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Autores principales: Periasamy, Sivakumar, Porter, Kristen A., Atianand, Maninjay K., T. Le, Hongnga, Earley, Sarah, Duffy, Ellen B., Haller, Matthew C., Chin, Heather, Harton, Jonathan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512670/
https://www.ncbi.nlm.nih.gov/pubmed/28580947
http://dx.doi.org/10.1038/ncomms15564
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author Periasamy, Sivakumar
Porter, Kristen A.
Atianand, Maninjay K.
T. Le, Hongnga
Earley, Sarah
Duffy, Ellen B.
Haller, Matthew C.
Chin, Heather
Harton, Jonathan A.
author_facet Periasamy, Sivakumar
Porter, Kristen A.
Atianand, Maninjay K.
T. Le, Hongnga
Earley, Sarah
Duffy, Ellen B.
Haller, Matthew C.
Chin, Heather
Harton, Jonathan A.
author_sort Periasamy, Sivakumar
collection PubMed
description Pyrin domain-only proteins (POPs) are recently evolved, primate-specific proteins demonstrated in vitro as negative regulators of inflammatory responses. However, their in vivo function is not understood. Of the four known POPs, only POP2 is reported to regulate NF-κB-dependent transcription and multiple inflammasomes. Here we use a transgenic mouse-expressing POP2 controlled by its endogenous human promotor to study the immunological functions of POP2. Despite having significantly reduced inflammatory cytokine responses to LPS and bacterial infection, POP2 transgenic mice are more resistant to bacterial infection than wild-type mice. In a pulmonary tularaemia model, POP2 enhances IFN-γ production, modulates neutrophil numbers, improves macrophage functions, increases bacterial control and diminishes lung pathology. Thus, unlike other POPs thought to diminish innate protection, POP2 reduces detrimental inflammation while preserving and enhancing protective immunity. Our findings suggest that POP2 acts as a high-order regulator balancing cellular function and inflammation with broad implications for inflammation-associated diseases and therapeutic intervention.
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spelling pubmed-55126702017-07-19 Pyrin-only protein 2 limits inflammation but improves protection against bacteria Periasamy, Sivakumar Porter, Kristen A. Atianand, Maninjay K. T. Le, Hongnga Earley, Sarah Duffy, Ellen B. Haller, Matthew C. Chin, Heather Harton, Jonathan A. Nat Commun Article Pyrin domain-only proteins (POPs) are recently evolved, primate-specific proteins demonstrated in vitro as negative regulators of inflammatory responses. However, their in vivo function is not understood. Of the four known POPs, only POP2 is reported to regulate NF-κB-dependent transcription and multiple inflammasomes. Here we use a transgenic mouse-expressing POP2 controlled by its endogenous human promotor to study the immunological functions of POP2. Despite having significantly reduced inflammatory cytokine responses to LPS and bacterial infection, POP2 transgenic mice are more resistant to bacterial infection than wild-type mice. In a pulmonary tularaemia model, POP2 enhances IFN-γ production, modulates neutrophil numbers, improves macrophage functions, increases bacterial control and diminishes lung pathology. Thus, unlike other POPs thought to diminish innate protection, POP2 reduces detrimental inflammation while preserving and enhancing protective immunity. Our findings suggest that POP2 acts as a high-order regulator balancing cellular function and inflammation with broad implications for inflammation-associated diseases and therapeutic intervention. Nature Publishing Group 2017-06-05 /pmc/articles/PMC5512670/ /pubmed/28580947 http://dx.doi.org/10.1038/ncomms15564 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Periasamy, Sivakumar
Porter, Kristen A.
Atianand, Maninjay K.
T. Le, Hongnga
Earley, Sarah
Duffy, Ellen B.
Haller, Matthew C.
Chin, Heather
Harton, Jonathan A.
Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title_full Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title_fullStr Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title_full_unstemmed Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title_short Pyrin-only protein 2 limits inflammation but improves protection against bacteria
title_sort pyrin-only protein 2 limits inflammation but improves protection against bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512670/
https://www.ncbi.nlm.nih.gov/pubmed/28580947
http://dx.doi.org/10.1038/ncomms15564
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