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Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors

BACKGROUND: Bacterial infection with the severe complication of sepsis is a frequent and serious condition, being a major cause of death worldwide. To cope with the plethora of occurring bacterial infections there is therefore an urgent need to identify molecular mechanisms operating during the host...

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Detalles Bibliográficos
Autores principales: Hagman, Ragnvi, Rönnberg, Elin, Pejler, Gunnar
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777310/
https://www.ncbi.nlm.nih.gov/pubmed/19956711
http://dx.doi.org/10.1371/journal.pone.0008039
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author Hagman, Ragnvi
Rönnberg, Elin
Pejler, Gunnar
author_facet Hagman, Ragnvi
Rönnberg, Elin
Pejler, Gunnar
author_sort Hagman, Ragnvi
collection PubMed
description BACKGROUND: Bacterial infection with the severe complication of sepsis is a frequent and serious condition, being a major cause of death worldwide. To cope with the plethora of occurring bacterial infections there is therefore an urgent need to identify molecular mechanisms operating during the host response, in order both to identify potential targets for therapeutic intervention and to identify biomarkers for disease. Here we addressed this issue by studying global gene expression in uteri from female dogs suffering from spontaneously occurring uterine bacterial infection. PRINCIPAL FINDINGS: The analysis showed that almost 800 genes were significantly (p<0.05) upregulated (>2-fold) in the uteri of diseased animals. Among these were numerous chemokine and cytokine genes, as well as genes associated with inflammatory cell extravasation, anti-bacterial action, the complement system and innate immune responses, as well as proteoglycan-associated genes. There was also a striking representation of genes associated with proteolysis. Robust upregulation of immunoglobulin components and genes involved in antigen presentation was also evident, indicating elaboration of a strong adaptive immune response. The bacterial infection was also associated with a significant downregulation of almost 700 genes, of which various homeobox and zinc finger transcription factors were highly represented. CONCLUSIONS/SIGNIFICANCE: Together, these finding outline the molecular patterns involved in bacterial infection of the uterus. The study identified altered expression of numerous genes not previously implicated in bacterial disease, and several of these may be evaluated for potential as biomarkers of disease or as therapeutic targets. Importantly, since humans and dogs show genetic similarity and develop diseases that share many characteristics, the molecular events identified here are likely to reflect the corresponding situation in humans afflicted by similar disease.
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spelling pubmed-27773102009-12-03 Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors Hagman, Ragnvi Rönnberg, Elin Pejler, Gunnar PLoS One Research Article BACKGROUND: Bacterial infection with the severe complication of sepsis is a frequent and serious condition, being a major cause of death worldwide. To cope with the plethora of occurring bacterial infections there is therefore an urgent need to identify molecular mechanisms operating during the host response, in order both to identify potential targets for therapeutic intervention and to identify biomarkers for disease. Here we addressed this issue by studying global gene expression in uteri from female dogs suffering from spontaneously occurring uterine bacterial infection. PRINCIPAL FINDINGS: The analysis showed that almost 800 genes were significantly (p<0.05) upregulated (>2-fold) in the uteri of diseased animals. Among these were numerous chemokine and cytokine genes, as well as genes associated with inflammatory cell extravasation, anti-bacterial action, the complement system and innate immune responses, as well as proteoglycan-associated genes. There was also a striking representation of genes associated with proteolysis. Robust upregulation of immunoglobulin components and genes involved in antigen presentation was also evident, indicating elaboration of a strong adaptive immune response. The bacterial infection was also associated with a significant downregulation of almost 700 genes, of which various homeobox and zinc finger transcription factors were highly represented. CONCLUSIONS/SIGNIFICANCE: Together, these finding outline the molecular patterns involved in bacterial infection of the uterus. The study identified altered expression of numerous genes not previously implicated in bacterial disease, and several of these may be evaluated for potential as biomarkers of disease or as therapeutic targets. Importantly, since humans and dogs show genetic similarity and develop diseases that share many characteristics, the molecular events identified here are likely to reflect the corresponding situation in humans afflicted by similar disease. Public Library of Science 2009-11-26 /pmc/articles/PMC2777310/ /pubmed/19956711 http://dx.doi.org/10.1371/journal.pone.0008039 Text en Hagman et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hagman, Ragnvi
Rönnberg, Elin
Pejler, Gunnar
Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title_full Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title_fullStr Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title_full_unstemmed Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title_short Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors
title_sort canine uterine bacterial infection induces upregulation of proteolysis-related genes and downregulation of homeobox and zinc finger factors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777310/
https://www.ncbi.nlm.nih.gov/pubmed/19956711
http://dx.doi.org/10.1371/journal.pone.0008039
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