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.
N1 - Funding Information:
The authors have the following interests: This project was supported by Pfizer Inc. Dr. Wunderink has received an investigator-initiated grant, participated in a clinical trial, and is a member of a data safety monitoring board with unrelated compounds/diagnostic tests for Pfizer. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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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U2 - 10.1371/journal.pone.0067994
DO - 10.1371/journal.pone.0067994
M3 - Article
C2 - 23826353
AN - SCOPUS:84879535173
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 6
M1 - e67994
ER -