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Mol Med. 2010 May-Jun;16(5-6):188-98. doi: 10.2119/molmed.2009.00166. Epub 2010 Feb 8.

Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice.

Author information

1
Cardiovascular Biology Program, Department of Pharmacology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore.

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.

PMID:
20454520
PMCID:
PMC2864813
DOI:
10.2119/molmed.2009.00166
[Indexed for MEDLINE]
Free PMC Article

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