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

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.
AuthorsAkhil Hegde, Ramasamy Tamizhselvi, Jayapal Manikandan, Alirio J Melendez, Shabbir M Moochhala, Madhav Bhatia
JournalMolecular medicine (Cambridge, Mass.) (Mol Med) 2010 May-Jun Vol. 16 Issue 5-6 Pg. 188-98 ISSN: 1528-3658 [Electronic] England
PMID20454520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemokines
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Protein Precursors
  • Tachykinins
  • preprotachykinin
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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