RGD Reference Report - Reduced PPARalpha Expression is Associated With Decreased Survival and Increased Tissue Bacterial Load in Sepsis. - Rat Genome Database

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Reduced PPARalpha Expression is Associated With Decreased Survival and Increased Tissue Bacterial Load in Sepsis.

Authors: Standage, SW  Caldwell, CC  Zingarelli, B  Wong, HR 
Citation: Standage SW, etal., Shock. 2011 Nov 15.
RGD ID: 5562037
Pubmed: PMID:22089192   (View Abstract at PubMed)
PMCID: PMC3261332   (View Article at PubMed Central)
DOI: DOI:10.1097/SHK.0b013e31823f1a00   (Journal Full-text)

ABSTRACT: The peroxisome-proliferator activated receptor alpha (PPARalpha) is a member of the nuclear receptor family with many important physiologic roles related to metabolism and inflammation. Previous research in pediatric patients with septic shock revealed that genes corresponding to the PPARalpha signaling pathway are significantly downregulated in a subgroup of children with more severe disease. In this study, PPARalpha expression analysis using whole blood derived RNA revealed that PPARalpha expression was decreased in patients with septic shock and that the magnitude of that decrement correlated with the severity of disease. In a mouse model of sepsis, induced by cecal ligation and puncture (CLP), knockout mice lacking PPARalpha had decreased survival compared to wild type animals. Plasma cytokine analysis demonstrated decreased levels of IL-1beta, IL-6, IL-17, KC, MCP-1, MIP-2, and TNFalpha at 24 hours in PPARalpha knockout animals. Cell surface markers of activation on splenic dendritic cells, macrophages, and CD8 T-cells were reduced in PPARalpha null animals and the bacterial load in lung and splenic tissues was increased. These data indicate that reduced or absent PPARalpha expression confers a survival disadvantage in sepsis and that PPARalpha plays a role in maintaining appropriate immune functions during the sepsis response.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPARAHumanSepsis severityIEP RNA:decreased expression:blood:associated with more severe diseaseRGD 
PparaRatSepsis severityISOPpara (Mus musculus)DNA:knockout::associated with more severe disease (mouse)RGD 
PparaMouseSepsis severityIAGP DNA:knockout::associated with more severe diseaseRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppara  (peroxisome proliferator activated receptor alpha)

Genes (Mus musculus)
Ppara  (peroxisome proliferator activated receptor alpha)

Genes (Homo sapiens)
PPARA  (peroxisome proliferator activated receptor alpha)


Additional Information