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Updated: Jun 13, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice
Akhil Hegde1, Ramasamy Tamizhselvi, Jayapal Manikandan
1Cardiovascular 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.
Insights
Deletion of the substance P gene (PPTA) in mice reduced sepsis-induced lung injury. Gene expression analysis revealed altered inflammatory and immune responses in knockout mice, suggesting a protective mechanism against sepsis.
Area of Science:
- Immunology
- Genetics
- Pulmonary Medicine
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
- Substance P, encoded by the preprotachykinin-A (PPTA) gene, plays a role in inflammation and immune responses.
- Previous studies suggest PPTA deletion protects against sepsis-induced lung injury and mortality.
Purpose of the Study:
- To investigate the differential gene expression profiles in mouse lung tissue during early sepsis.
- To determine the effect of PPTA gene deletion on these expression profiles.
- To gain biological insight into the protective mechanisms of PPTA knockout in sepsis.
Main Methods:
- Microarray analysis of lung tissue gene expression in wild-type and PPTA-knockout mice 8 hours after inducing sepsis via cecal ligation and puncture.
- Comparison of gene expression between septic and sham control groups.
- Validation of microarray data using semiquantitative RT-PCR.
Main Results:
- PPTA gene deletion significantly altered the expression of genes involved in inflammation and immunomodulation during sepsis.
- Elevated expression of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL1RN) was observed in PPTA-knockout septic mice.
- Microarray data indicated potentially beneficial early inflammatory gene expression changes in PPTA-knockout mice, possibly aiding infection resolution without excessive immunosuppression.
Conclusions:
- Genetic deletion of substance P (PPTA) modulates pulmonary gene expression during early sepsis.
- These alterations in inflammatory and immune gene profiles may contribute to the observed protection against lung injury and mortality in PPTA-knockout mice.
- Genome-wide expression profiling provides crucial insights into the complex mediator roles in sepsis.
