Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling time course of mouse lung after in-vivo intrapulmonary administration of CpG.

ABSTRACT: Analysis of whole mouse lung gene expression signature induced by in-vivo intrapulmonary administration of CpG. CpG-containing oligodeoxynucleotides are potent mucosal adjuvants and effective as stand-alone treatment of respiratory infections in mice.

ORGANISM(S): Mus musculus

SUBMITTER: Elisabetta Monaci

PROVIDER: E-TABM-823 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Staphylococcus Enterotoxin B (SEB) is an exotoxin produced by Staphylococcus aureus. It is a public health threat during nosocomial infections. It is also considered as a biological weapon. The Centers for Disease Control and Prevention (CDC) lists SEB as a category B agent of Biodefence. SEB is easily aerosolized and can enter the host through inhalation which could lead to Acute Lung Injury (ALI) and in severe cases, it may result in multiple organ failure, shock and death. It is considered to be a Super-antigen as it activates a large number (30%) of T cells and results in the production of cytokines SEB binds directly to the non polymorphic region of MHC Class II which is expressed on antigen presenting cells and this complex activates T cells expressing a specific variable region of the β chain (Vβ8) of the T cell receptor (TCR). Thus, inhalation of SEB leads to recruitment of immune cells into the lung and secretion of pro-inflammatory cytokines which results in severe damage to the lung by increasing the permeability, and induction of respiratory failure. MicroRNA (miRNAs) is considered one of the mechanisms by which the epigenetic regulation happens. MicroRNA are noncoding small RNAs that have recently been shown to play a role in gene expression. The action of miRNA is dependent on its binding to 3’ Untranslated Region (3’UTR) of mRNA resulting in transcriptional or translational repression. Specifically, the efficacy of gene silencing is determined by the interaction of miRNA seed sequence with the target mRNA. Endocannabinoids are lipid molecules produced endogenously by host cells and bind to cannabinoid receptors, CB1 and CB2. N-Arachidonoylethanolamide or anandamide (AEA) is an endocannabinoid that has been shown to have immunomodulatory effects by our lab and others, although the precise mechanism is not clear. So far through my research, I found that Endocannabinoid is involved in a very unique way in the anti-inflammatory response through upregulation of many anti-inflammatory genes such as FOXP3, ARG1, and IL-10 that targeted by miRNA23a-3p and miRNA 34a-5p as well as the anti-inflammatory phenotype population as it show in the RT-PCR and flow cytometry results.

Project description:BACKGROUND & AIM: Sessile serrated adenoma/polyps (SSA/Ps) are the likely culprit of ~20% colon cancers but they are molecularly poorly understood. We investigated their epigenetic phenotype using high-throughput analysis of DNA methylation and gene expression. METHODS: 17 SSA/Ps and, as a comparative group, 15 conventional adenomas (all with matched samples of normal mucosa) were prospectively collected during colonoscopy. DNA from the 64 tissues was analyzed, via bisulfite next generation sequencing, for methylation at ~2.7 million CpG sites located prevalently in gene regulatory regions spanning 80.5Mb (~2.5% of the genome). The transcriptome of these samples was also investigated using RNA sequencing. An independent series of 61 archival lesions was used for targeted verification of DNA methylation. RESULTS: Both SSA/Ps and conventional adenomas showed a profound remodelling of their methylome. Cytosine hypermethylation was more pervasive in SSA/Ps than adenomas, in terms of number of hypermethylated regions (22,147 vs 15,965, respectively) and genes (4938 vs 3443, respectively). In addition, the extent of hypermethylation in a given region was higher in SSA/Ps than adenomas. This methylation pattern of SSA/Ps was reminiscent of the CpG island methylator phenotype (CIMP) of their descendant cancers. We have called this phenotype proto-CIMP since most of the hypermethylation occurred in CpG islands and shores. SSA/Ps were also protected from a wave of demethylation that instead occurred in adenomas outside of CpG islands/shores (4288 vs 18,417 hypomethylated regions in SSAPs vs adenomas). Verification studies of six hypermethylated regions demonstrated the high potential of DNA methylation markers for predicting the diagnosis of SSA/Ps and/or adenomas. Proto-CIMP of SSA/Ps was surprisingly associated with a higher number of up- (618) than downregulated (349) genes, while adenomas showed the opposite trend (516 up- vs 712 downregulated genes). CONCLUSIONS: The epigenetic landscape of SSA/Ps differs substantially from that of conventional adenomas. This huge amount of epigenetic variation represents a rich source of promising diagnostic tools, such as novel DNA markers or histologic stainings, for the tailored management of the two most frequent colon cancer precursors.

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Transcription profiling time course of mouse lung after in-vivo intrapulmonary administration of CpG.

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