Temporal dynamics of gene expression in the lung in a baboon model of E. coli sepsis.
BACKGROUND
Bacterial invasion during sepsis induces disregulated systemic responses that could lead to fatal lung failure. The purpose of this study was to relate the temporal dynamics of gene expression to the pathophysiological changes in the lung during the first and second stages of E. coli sepsis in baboons.


RESULTS
Using human oligonucleotide microarrays, we have explored the temporal changes of gene expression in the lung of baboons challenged with sublethal doses of E. coli. Temporal expression pattern and biological significance of the differentially expressed genes were explored using clustering and pathway analysis software. Expression of selected genes was validated by real-time PCR. Cytokine levels in tissue and plasma were assayed by multiplex ELISA. Changes in lung ultrastructure were visualized by electron microscopy. We found that genes involved in primary inflammation, innate immune response, and apoptosis peaked at 2 hrs. Inflammatory and immune response genes that function in the stimulation of monocytes, natural killer and T-cells, and in the modulation of cell adhesion peaked at 8 hrs, while genes involved in wound healing and functional recovery were upregulated at 24 hrs.


CONCLUSIONS
The analysis of gene expression modulation in response to sepsis provides the baseline information that is crucial for the understanding of the pathophysiology of systemic inflammation and may facilitate the development of future approaches for sepsis therapy.
Zhu
Hua
H
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. hua-zhu@omrf.ouhsc.edu <hua-zhu@omrf.ouhsc.edu>
Tang
Yuhong
Y
Ivanciu
Lacramioara
L
Centola
Michael
M
Lupu
Cristina
C
Taylor
Fletcher B
FB
Lupu
Florea
F
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D010215:Papio; D018805:Sepsis / Q000235:genetics* / Q000276:immunology; D049490:Systems Biology; D013997:Time Factors; D014945:Wound Healing / Q000235:genetics