Abstract |
Deletion of mouse preprotachykinin-A (PPTA), which encodes mainly for neuropeptide substance P, has been shown to protect against lung injury and mortality in sepsis. This study explored microarray-based differential gene expression profiles in mouse lung tissue 8 h after inducing microbial sepsis and the effect of PPTA gene deletion. A range of genes differentially expressed (more than two-fold) in microarray analysis was assessed, comparing wild-type and PPTA-knockout septic mice with their respective sham controls, and the data were further validated. Genetic deletion of substance P resulted in a significantly different expression profile of genes involved in inflammation and immunomodulation after the induction of sepsis, compared with wild-type mice. Interestingly, apart from the various proinflammatory mediators, the antiinflammatory cytokine interleukin-1 receptor antagonist gene (IL1RN) was also elevated much more in PPTA(-/-) septic mice. In addition, semiquantitative RT-PCR analysis supported the microarray data. The microarray data imply that the elevated levels of inflammatory gene expression in the early stages of sepsis in PPTA-knockout mice are possibly aimed to resolve the infection without excessive immunosuppression. As scientists are divided over the effects of pro- and antiinflammatory mediators in sepsis, it seems prudent to define the status depending on a complete genome profile. This is the first report exploring pulmonary gene expression profiles using microarray analysis in PPTA-knockout mice subjected to cecal ligation and puncture-induced sepsis and providing additional biological insight into the protection received against lung injury and mortality.
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Authors | Akhil Hegde, Ramasamy Tamizhselvi, Jayapal Manikandan, Alirio J Melendez, Shabbir M Moochhala, Madhav Bhatia |
Journal | Molecular medicine (Cambridge, Mass.)
(Mol Med)
2010 May-Jun
Vol. 16
Issue 5-6
Pg. 188-98
ISSN: 1528-3658 [Electronic] England |
PMID | 20454520
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chemokines
- Il1rn protein, mouse
- Interleukin 1 Receptor Antagonist Protein
- Protein Precursors
- Tachykinins
- preprotachykinin
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Topics |
- Analysis of Variance
- Animals
- Bacteremia
(genetics, metabolism, microbiology)
- Chemokines
(genetics, metabolism)
- Disease Models, Animal
- Gene Expression Profiling
- Inflammation
(genetics, metabolism)
- Interleukin 1 Receptor Antagonist Protein
(genetics, metabolism)
- Lung Diseases
(genetics, metabolism, microbiology)
- Mice
- Mice, Knockout
- Oligonucleotide Array Sequence Analysis
- Protein Precursors
(deficiency, genetics, metabolism)
- Reproducibility of Results
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Tachykinins
(deficiency, genetics, metabolism)
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