Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse splenic CD4+ cells after surgical induction of sepsis vs. controls reveals a distinct transcriptional response 6 hours after sepsis induction

ABSTRACT: Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. CD4+ splenocytes were isolated 6h after the surgical induction of sepsis for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain a homogeneous cell population in order to reduce any effects of cellular heterogeneity on expression profiles. To that end, immunomagnetic negative selection was used to enrich CD4+ splenocyte populations to ~91%. (n=5 biological replicates each CLP and sham)

ORGANISM(S): Mus musculus

DISEASE(S): septic peritonitis

SUBMITTER: Jonathan McDunn

PROVIDER: E-GEOD-4479 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis.

McDunn Jonathan E JE Turnbull Isaiah R IR Polpitiya Ashoka D AD Tong Alice A MacMillan Sandra K SK Osborne Dale F DF Hotchkiss Richard S RS Colonna Marco M Cobb J Perren JP

Journal of the American College of Surgeons 20060901 3

<h4>Background</h4>In animal and human autopsy studies of sepsis, CD4+ splenocytes either undergo apoptosis or are polarized to the Th2 effector subtype. In mice, these changes occur within 24 hours of the onset of sepsis. Preventing the loss of CD4+ T cells and the Th2-polarization of CD4+ T cells provides a significant survival advantage in mouse models of sepsis. The molecular mechanism(s) for the phenotypic changes of splenic CD4+ T cells in sepsis are not well understood.<h4>Study design</h ...[more]

PMID: 16931309

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Project description:Background: Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. Methods: The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by TMT-LC–MS/MS-based proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. Results: Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 were confirmed by Western blot. Conclusions: Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) can potentially be diagnosis biomarkers, therapeutic targets, and prognosis indicators of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.

Dataset Information

Transcription profiling of mouse splenic CD4+ cells after surgical induction of sepsis vs. controls reveals a distinct transcriptional response 6 hours after sepsis induction

Publications

Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis.

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