Host Responses to Sepsis Vary in Different Low-Lethality Murine Models
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: M Cecilia Lopez
PROVIDER: E-GEOD-55238 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The CS and CLP murine models of intra-abdominal sepsis have unique transcriptomic respones 2 hrs, 1 and 3 days after sepsis
2014-02-21 | GSE55238 | GEO
Project description:Sepsis induces systemic stress by augmenting inflammatory and pro-coagulant responses resulting in microvascular dysfunction and end organ failure, events modulated by the Protein C pathway. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene transcription yet their role in sepsis remains poorly defined. We hypothesized that aPC selectively alters the expression of specific miRNAs implicated in protection of hepatic function during septic shock. Male Sprague-Dawley rats underwent sham surgery or cecal ligation and puncture (CLP). Twenty-four later, animals were randomized and treated with aPC (1mg/kg) or vehicle (0.9% (w/v) saline) via an indwelling venous catheter at 12 hour intervals for 24 hours. Gene array was performed on hepatic RNA to determine miRNA expression, and predicted mRNA targets determined using a bioinformatics approach. Of 351 rat miRNAs examined by microarray hybridization, 17 were highly expressed during sepsis and restored to basal levels after aPC treatment. In silico analysis identified 9 miRNAs significantly regulating target genes of the focal adhesion pathway. These data suggest aPC treatment coordinates beneficial cytoprotective effects during sepsis by modulating miRNA expression. While translational effects remain to be fully elucidated in a clinical setting, we demonstrate herein the potential experimental and computational benefits for use of microRNA analysis in sepsis. 12 samples were analyzed. Microarray experiments were performed, in which liver tissue was harvested from variuous groups (Sham+Vehicle, Sham+aPC, CLP+Vehicle, CLP+aPC; n=3/group) and pooled.
2014-12-20 | E-GEOD-34790 | biostudies-arrayexpress
Project description:Expression data from Total RNA extracted from murine spleen. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis. To identify the molecular changes associated with decreased inflammation in CLP-injured mice treated with MSCs, we analyzed the gene expression profiles from spleens collected at 28 hours from 4 animals per group: sham/saline, CLP/saline, and CLP/MSCs.
2010-11-22 | E-GEOD-24357 | biostudies-arrayexpress
Project description:Expression data from Total RNA extracted from murine spleen, liver, lungs, kidneys and hearts. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis. To identify the molecular changes associated with decreased inflammation in CLP-injured mice treated with MSCs, we analyzed the gene expression profiles from spleens, liver, lungs, kidneys and heart collected at 28 hours from 4 animals per group: sham/saline, CLP/saline, and CLP/MSCs.
2012-12-31 | E-GEOD-40180 | biostudies-arrayexpress
Project description:To profile the expression of circulating microRNAs (miRNAs) of mice in experimental sepsis by cecal ligation and puncture (CLP), the whole blood samples were obtained from C57BL/6 mice at 4, 8, and 24 h following CLP for miRNA expression analysis using a miRNA array (The Mouse & Rat miRNA OneArray® v3). Briefly, mice were anesthetized with a combination of ketamine and xylazine as the anesthetic/analgesic agents and a midline abdominal incision was made. The cecum was mobilized, ligated in the middle of cecum below the ileocecal valve, punctured once with a 21 G needle, and a little stool was squeeze out of the cecum to induce polymicrobial peritonitis. The abdominal wall was closed in two layers. Sham-operated mice underwent the same procedure, including opening the peritoneum and exposing the bowel, but without ligation and needle perforation of the cecum. the whole blood samples were obtained from C57BL/6 mice at 4, 8, and 24 h following CLP for miRNA expression analysis using a miRNA array (The miRNA OneArray® v3).
2015-05-15 | E-GEOD-47094 | biostudies-arrayexpress
Project description:To investigate the role of TSPO in the sequelae of sepsis induced by cecal ligation and puncture (CLP), hippocampal gene expression changes after CLP surgery were examined in wild-type and TSPO KO mice
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Project description:Mice underwent cecal ligation and puncture (19 GA with concurrent administration of imipenem), sham operation, or were unoperated. 14 days after operation, microglia were isolated by fluorescent activated cell sorting for CD11b+/CD45mid/CD64+ cells. For each sample, the brains of 3 mice were pooled. RNA was then isolated for transcriptome analysis.
2016-07-01 | E-MTAB-4180 | biostudies-arrayexpress
Project description:Background: We hypothesized that spleen microarray gene expression profiles analyzed with contemporary pathway analysis software would provide molecular pathways of interest and target genes that might help explain the affect of bcl-2 on improving survival during sepsis. Methods: Two mouse models of sepsis, cecal ligation and puncture and tracheal instillation of Pseudomonas aeruginosa, were tested in both wild-type mice and mice that overexpress bcl-2. Whole spleens were obtained 6 hours after septic injury. DNA microarray transcriptional profiles were obtained using the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity Pathway Analysis software was used to construct hypothetical transcriptional networks that changed in response to sepsis and expression of the bcl-2 transgene. Results: A conservative approach was used wherein only changes induced by both abdominal and pulmonary sepsis were studied. At 6 hours, sepsis induced alterations in the abundance of hundreds of spleen genes, including a number of proinflammatory mediators (e.g., IL-6). These sepsis-induced alterations were blocked by expression of the bcl-2 transgene. Network analysis implicated a number of bcl-2-related apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and mcl-1. Sepsis in bcl-2 transgenic animals resulted in alteration of RNA abundance for only a single gene, ceacam1. Conclusion: These findings are consistent with sepsis-induced alterations in the balance of pro- and anti-apoptotic transcriptional networks. In addition, our data suggest that the ability of bcl-2 overexpression to improve survival in sepsis in this model is related in part to prevention of sepsis-induced alterations in spleen transcriptional responses. Experiment Overall Design: To determine the splenic response in these lethal models of CLP and Pseudomonas pneumonia, microarray analysis was performed on each spleen harvested from wild-type animals 6 hours after CLP or tracheal instillation of bacteria. The responses of the CLP or Pseudomonas spleens were compared concurrently to those of the wild-type controls, sham laparotomy and tracheal instillation of saline, respectively. This study was repeated in animals overexpressing bcl-2. Thus, the splenocyte effect of sepsis secondary to CLP (n=6) or Pseudomonas pneumonia (n=5) could be determined compared to their controls (n=6 and 5, respectively), and the effect of bcl-2 overexpression in turn also could be determined in both CLP (n=5) and pneumonia models (n=5) compared to controls (n=5 and 5, respectively).
2008-06-14 | E-GEOD-5811 | biostudies-arrayexpress
Project description:Acute phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and anti-inflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a murine model for polymicrobial sepsis we show here that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6-family cytokines, dramatically increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through signal transducer and activator of transcription (Stat)3 was required to control systemic inflammation. Notably, hepatic gp130/Stat3 activation was also a prerequisite to facilitate mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for anti-inflammatory properties in cancer. We show that MDSCs were critical to regulate innate inflammation and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. We identified serum amyloid A and Cxcl-1/KC as hepatic acute phase genes that cooperatively promoted MDSC mobilization, accumulation and survival. Administration of these proteins efficiently elevated MDSC numbers and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through acute phase proteins critically controls inflammatory responses during infection. Control [gp130f/f] and liver-specific Gp130 knockout [gp130delta(hepa)] mice were subjected to polymicrobial sepsis. Twelve hours after induction of sepsis mice were sacrificed and livers were removed. For control treatment mice were sacrified without any prior treatment. Total RNA was isolated and subjected to gene expression profiling.
2010-06-08 | E-GEOD-22009 | biostudies-arrayexpress
Project description:Because the immune regulation in survivor after sepsis (an immune dysregulation from severe infection) might be applied for treatment, survivors and moribund mice after cecal liga-tion and puncture (CLP) and in vitro experiments on macrophages were explored. Most of the parameters in survivors (5-days post-CLP) were normalized, except for the slightly increase in alanine transaminase, IL-10, lipopolysaccharide (LPS) and gut leakage (FITC-dextran assay), with the enhanced adaptive immunity; serum immunoglobulin (using serum protein electrophoresis) and activated immune cells in spleens (flow cytometry analysis). Then, a clue to surviving sepsis may be effective innate immunity regulation by adaptive immune responses. Indeed, soluble heat aggregated immunoglobulin (sHA-Ig, a representative of immune complex) in LPS-activated macrophages reduced supernatant cytokines and down-regulated proteins in sev-eral processes (using proteomic analysis). As a proof of concept, intravenous immunoglobulin (IVIG) attenuated sepsis severity in CLP mice as evaluated by serum creatinine, ALT, serum cy-tokines, spleen apoptosis (24 h post-CLP) and 48 h survival analysis. In conclusion, immuno-globulin may play a role in sepsis immune hyper-responsiveness. Despite the debate over IVIG's use in sepsis, adequate selection criteria for sepsis patients who may benefit the most from IVIG could lead to an increase use of this clinically viable treatment.
2022-02-22 | PXD027471 | Pride