Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling

A Mouse MRSA Pneumonia Model

Jiwang Chen*, Gang Feng, Yang Song, Juliane B. Wardenburg, Simon Lin, Ichiro Inoshima, Michael Otto, Richard G Wunderink

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background:Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.Methods:A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.Results:LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.Conclusion:LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.

Original languageEnglish (US)
Article numbere67994
JournalPloS one
Volume8
Issue number6
DOIs
StatePublished - Jun 27 2013

Fingerprint

Linezolid
Gene Expression Profiling
Methicillin-Resistant Staphylococcus aureus
Gene expression
pneumonia
Pneumonia
lungs
gene expression
Lung
mice
Bronchoalveolar Lavage Fluid
immune response
interferons
Interferons
Interleukin-6
cytokines
animal models
Cytokines
Gene Expression
therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chen, Jiwang ; Feng, Gang ; Song, Yang ; Wardenburg, Juliane B. ; Lin, Simon ; Inoshima, Ichiro ; Otto, Michael ; Wunderink, Richard G. / Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling : A Mouse MRSA Pneumonia Model. In: PloS one. 2013 ; Vol. 8, No. 6.
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title = "Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model",
abstract = "Background:Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.Methods:A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.Results:LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.Conclusion:LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.",
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Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling : A Mouse MRSA Pneumonia Model. / Chen, Jiwang; Feng, Gang; Song, Yang; Wardenburg, Juliane B.; Lin, Simon; Inoshima, Ichiro; Otto, Michael; Wunderink, Richard G.

In: PloS one, Vol. 8, No. 6, e67994, 27.06.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling

T2 - A Mouse MRSA Pneumonia Model

AU - Chen, Jiwang

AU - Feng, Gang

AU - Song, Yang

AU - Wardenburg, Juliane B.

AU - Lin, Simon

AU - Inoshima, Ichiro

AU - Otto, Michael

AU - Wunderink, Richard G

PY - 2013/6/27

Y1 - 2013/6/27

N2 - Background:Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.Methods:A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.Results:LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.Conclusion:LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.

AB - Background:Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.Methods:A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.Results:LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.Conclusion:LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.

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