Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IDR-1018 treatment of mice infected with Plasmodium berghei, spleen and brain expression data

ABSTRACT: Severe malaria encompasses a range of syndromes manifesting systemically or in diverse organs. These are believed to represent the end-stage processes of local parasite sequestration and inflammatory cascades. Classical anti-malarial drugs target parasites only. In treatment of severe disease, adjunctive therapies capable of controlling the inflammatory processes could be beneficial. Innate defense regulator (IDR) peptides display multiple immune modulatory activities. In this study, we assessed peptide IDR-1018, which shows promise as an anti-inflammatory drug, as a lead candidate for adjunctive host-directed therapy of established disease in the P. berghei ANKA model of experimental cerebral malaria (ECM). Intravenously administered IDR-1018 partially protected mice from ECM both prophylactically and in adjunctive treatment with classical anti-malarial drugs. We used transcriptional data from spleens and brains taken early in infection (day 3) of prophylactically treated mice to investigate the protective mechanisms. The microarrays compared spleens and brains from nine IDR-1018 i.v. treated, infected mice (IDR-1018-treated infected) with three saline i.v. treated infected mice (saline-treated infected) and three uninfected untreated control mice (controls). RNA samples were hybridized in randomized order to five Illumina WG-6 v2 BeadChips . No technical replicates were performed.

ORGANISM(S): Mus musculus

SUBMITTER: Gordon Smyth

PROVIDER: E-GEOD-32007 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

IDR-1018 treatment of mice infected with Plasmodium berghei, spleen and brain expression data

Project description:Severe malaria encompasses a range of syndromes manifesting systemically or in diverse organs. These are believed to represent the end-stage processes of local parasite sequestration and inflammatory cascades. Classical anti-malarial drugs target parasites only. In treatment of severe disease, adjunctive therapies capable of controlling the inflammatory processes could be beneficial. Innate defense regulator (IDR) peptides display multiple immune modulatory activities. In this study, we assessed peptide IDR-1018, which shows promise as an anti-inflammatory drug, as a lead candidate for adjunctive host-directed therapy of established disease in the P. berghei ANKA model of experimental cerebral malaria (ECM). Intravenously administered IDR-1018 partially protected mice from ECM both prophylactically and in adjunctive treatment with classical anti-malarial drugs. We used transcriptional data from spleens and brains taken early in infection (day 3) of prophylactically treated mice to investigate the protective mechanisms.

2012-04-09 | GSE32007 | GEO

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells (RNA-seq)

Project description:Genome-wide gene expression was measured in peripheral blood mononuclear cells (PBMCs) from patients with cystic fibrosis (CF) after treatment in vitro with the flagellin protein fliC, and/or synthetic peptide IDR-1018 to assess patterns of gene expression. The patterns of gene expression suggest that CF cells have a hyperinflammatory phenotype including dysfunctional autophagy processes. The synthetic peptide IDR-1018 attentuates this hyperinflammatory phenotype. Total RNA was obtained from PBMCs obtained from CF patients after treatment with the fliC flagellin protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.

2012-11-20 | E-GEOD-35394 | biostudies-arrayexpress

Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation

Project description:Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defenses peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on macrophages/monocytes. Here we measured the effect of IDR-1018 on macrophage gene expression during differentiation. Differentiation in the presence of IDR-1018 induced a unique signature of immune responses suggesting that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. RNA-seq was performed using the Illumina Genome Analyzer IIx platform. Monocytes were isolated from 3 healthy donors, and left unstimulated or stimulated for 4 hours with 20 μg/ml IDR-1018. For library preparation, 500 ng of total RNA was processed according to the Illumina TruSeq RNA sample preparation guide (Illumina catalogue number FC-122-1002). Briefly, mRNA was purified using poly-dT beads, followed by synthesis of the first and second cDNA strands, end repair addition of an poly-A overhang, and ligation of adapters and unique barcodes, as per the manufacturer’s instructions. DNA enrichment was carried out via a 15-cycle PCR. Following quantification, 8 pM of dsDNA was used for cluster generation on a CBOT instrument (Illumina, San Diego, CA). RNA sequencing was done on a GAIIx instrument (Illumina), performed as a single read run with 51 amplification cycles. Data processing was carried out in house, using CASAVA to convert raw data and demultiplex to FASTQ sequence files. Reads were aligned to the reference genome using TOPHAT, and then mapped to genes using the Bioconductor package GenomeRanges.

2013-10-16 | E-GEOD-40131 | biostudies-arrayexpress

Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation

2013-10-16 | GSE40131 | GEO

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells

Project description:Genome-wide gene expression was measured in two cell lines: CF bronchial epithelial cell line IB3-1 (compound heterozygote for the ΔF508 and W1282X CFTR mutations) and the isogenic, CFTR-corrected C38 cell line, after treatment with the flagellin protein FliC, and/or synthetic peptide IDR-1018. Total RNA was obtained from cell lines representing CF and normal epithelial cells after treatment with the fliC protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.

2012-11-05 | E-GEOD-35391 | biostudies-arrayexpress

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells (RNA-seq)

2012-11-20 | GSE35394 | GEO

Neuroprotection by a novel immunomodulatory peptide [P9 mice]

Project description:Perinatal brain injury is a major clinical problem associated with high neonatal mortality and morbidity and an increased risk of life-long chronic disabilities. Despite improved survival rates, the absolute numbers of neurological handicaps of perinatal origin have not decreased. There is currently no pharmacological treatment providing neuroprotction in neonates. As activation of the innate immune response is a key contributing factor to brain injury in both term and preterm infants we investigated the therapeutic potential of novel immunomodulatory innate defence regulator peptides (IDRs) in perinatal brain injury. IDR-1018 significantly reduced the production of inflammatory mediators by LPS-stimulated microglia cells in vitro. IDR-1018 was also neuroprotective in a clinically-relevant animal model of neonatal brain injury, exerting effects on regulatory molecules of TLR-, Ca2+- and p53-signaling. Of utmost importance, IDR-1018 markedly protected both white and grey brain matter when administered after the injury, thus has tremendous applicability to the clinical setting. Here we demonstrate for the first time that peripheral administration of an immunomodulatory peptide is neuroprotective in vivo in a clinically relevant model of perinatal brain damage.

2016-09-17 | GSE36215 | GEO

Neuroprotection by a novel immunomodulatory peptide [adult mice]

2016-09-17 | GSE51026 | GEO

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells

2012-11-05 | GSE35391 | GEO