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Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia
Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did requi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600913/ https://www.ncbi.nlm.nih.gov/pubmed/23401489 http://dx.doi.org/10.1084/jem.20120260 |
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author | Choi, Sun-Mi McAleer, Jeremy P. Zheng, Mingquan Pociask, Derek A. Kaplan, Mark H. Qin, Shulin Reinhart, Todd A. Kolls, Jay K. |
author_facet | Choi, Sun-Mi McAleer, Jeremy P. Zheng, Mingquan Pociask, Derek A. Kaplan, Mark H. Qin, Shulin Reinhart, Todd A. Kolls, Jay K. |
author_sort | Choi, Sun-Mi |
collection | PubMed |
description | Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 γ), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3γ bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3γ rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3γ. |
format | Online Article Text |
id | pubmed-3600913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36009132013-09-11 Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia Choi, Sun-Mi McAleer, Jeremy P. Zheng, Mingquan Pociask, Derek A. Kaplan, Mark H. Qin, Shulin Reinhart, Todd A. Kolls, Jay K. J Exp Med Article Pulmonary Staphylococcus aureus (SA) infections are a public health concern and a major complication of hyper-IgE syndrome, caused by mutations in STAT3. In contrast to previous findings of skin infection, we observed that clearance of SA from the lung did not require T, B, or NK cells but did require Stat3 activation. Immunohistochemistry showed robust Stat3 phosphorylation in the lung epithelium. We identified that a critical Stat3 target gene in lung epithelium is Reg3g (regenerating islet-derived 3 γ), a gene which is highly expressed in gastrointestinal epithelium but whose role in pulmonary host defense is uncharacterized. Stat3 regulated Reg3g transcription through direct binding at the Reg3g promoter region. Recombinant Reg3γ bound to SA and had both bacteriostatic and bactericidal activity in a dose-dependent fashion. Stat3 inhibition in vivo reduced Reg3g transcripts in the lung, and more importantly, recombinant Reg3γ rescued mice from defective SA clearance. These findings reveal an antibacterial function for lung epithelium through Stat3-mediated induction of Reg3γ. The Rockefeller University Press 2013-03-11 /pmc/articles/PMC3600913/ /pubmed/23401489 http://dx.doi.org/10.1084/jem.20120260 Text en © 2013 Choi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Choi, Sun-Mi McAleer, Jeremy P. Zheng, Mingquan Pociask, Derek A. Kaplan, Mark H. Qin, Shulin Reinhart, Todd A. Kolls, Jay K. Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title | Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title_full | Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title_fullStr | Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title_full_unstemmed | Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title_short | Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia |
title_sort | innate stat3-mediated induction of the antimicrobial protein reg3γ is required for host defense against mrsa pneumonia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600913/ https://www.ncbi.nlm.nih.gov/pubmed/23401489 http://dx.doi.org/10.1084/jem.20120260 |
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