We are analyzing https://link.springer.com/article/10.1186/s13045-017-0406-2.

Title:
Analyses of caspase-1-regulated transcriptomes in various tissues lead to identification of novel IL-1β-, IL-18- and sirtuin-1-independent pathways | Journal of Hematology & Oncology
Description:
Background It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β, IL-18, and Sirt-1. The microarray datasets derived from various caspase-1 knockout tissues indicated that caspase-1 can significantly impact the transcriptome. However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. Therefore, we hypothesized that the effects of caspase-1 on transcriptome may be partially independent from IL-1β, IL-18, and Sirt-1. Methods To determine new global and tissue-specific gene regulatory effects of caspase-1, we took novel microarray data analysis approaches including Venn analysis, cooperation analysis, and meta-analysis methods. We used these statistical methods to integrate different microarray datasets conducted on different caspase-1 knockout tissues and datasets where caspase-1 downstream targets were manipulated. Results We made the following important findings: (1) Caspase-1 exerts its regulatory effects on the majority of genes in a tissue-specific manner; (2) Caspase-1 regulatory genes partially cooperates with genes regulated by sirtuin-1 during organ injury and inflammation in adipose tissue but not in the liver; (3) Caspase-1 cooperates with IL-1β in regulating less than half of the genes involved in cardiovascular disease, organismal injury, and cancer in mouse liver; (4) The meta-analysis identifies 40 caspase-1 globally regulated genes across tissues, suggesting that caspase-1 globally regulates many novel pathways; and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways. Conclusions Our findings suggest that caspase-1 regulates many new signaling pathways potentially via its known substrates and also via transcription factors and other proteins that are yet to be identified.
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Keywords {🔍}

caspase, genes, pubmed, sirt, expression, ilβ, article, gene, regulated, google, scholar, analysis, tissues, fig, cas, metaanalysis, datasets, tissue, central, microarray, effects, cell, liver, regulatory, significantly, data, pathways, adipose, globally, gse, cooperation, substrates, inflammasome, identified, mouse, protein, changed, pathway, including, fold, tissuespecific, venn, results, activation, regulate, metabolism, shown, table, inflammation, regulates,

Topics {✒️}

proinflammatory il-1beta-rich microparticles immunosuppressive/anti-inflammatory cytokines directly high-fat-diet feeding nf-kb-mediated inflammatory pathways il-1β transgene/treatment induced mature pro-inflammatory il-1β article download pdf pro-inflammatory cytokines il-1β caspase-1-dependent interleukin-1beta secretion xiao-feng yang mitochondria-mediated apoptosis pathway genome-wide association studies phosphatase-mediated de-phosphorylation il-1β treatment-induced genes degrading anti-inflammatory sirtuin-1 na+/ca2+-exchange protein 1 kinase-mediated protein phosphorylation il-1β-mediated signaling pathways hydroxy-delta-5-steroid dehydrogenase regulating antigen-specific cd8+ il-1β-related microarray datasets retinoic acid-inducible gene endothelial progenitor cells generating mature il-1β cytosolic multi-protein complexes serine-type endopeptidase activity zinc-finger double domain intra-cerebroventricular ifn-β pathway-based approach identifies il-1β including meg3 il-1β including gas5 caspase-1-promoted gene 4933413g19rik gene-deficient mouse samples interferon-inducible proteins member caspase-1-dependent mitochondrial damage caspase-1 activates il-1β uncharacterized protein-coding gene sirt1 activates mao full size image interferon-beta il-1β mononuclear cells withdrawn active caspase-1-mediated secretion sirt-1-regulated pathways globally caspase-1-mediated gene expression tissue-specific regulatory effects genome-wide comparison parallel meta-il-1β van diepen ja il-1β regulatory pathways il-1β regulatory genes

Questions {❓}

Caspase-1: is IL-1 just the tip of the ICEberg?
Muscle phosphorylase kinase deficiency: a neutral metabolic variant or a disease?

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      description:It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β, IL-18, and Sirt-1. The microarray datasets derived from various caspase-1 knockout tissues indicated that caspase-1 can significantly impact the transcriptome. However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. Therefore, we hypothesized that the effects of caspase-1 on transcriptome may be partially independent from IL-1β, IL-18, and Sirt-1. To determine new global and tissue-specific gene regulatory effects of caspase-1, we took novel microarray data analysis approaches including Venn analysis, cooperation analysis, and meta-analysis methods. We used these statistical methods to integrate different microarray datasets conducted on different caspase-1 knockout tissues and datasets where caspase-1 downstream targets were manipulated. We made the following important findings: (1) Caspase-1 exerts its regulatory effects on the majority of genes in a tissue-specific manner; (2) Caspase-1 regulatory genes partially cooperates with genes regulated by sirtuin-1 during organ injury and inflammation in adipose tissue but not in the liver; (3) Caspase-1 cooperates with IL-1β in regulating less than half of the genes involved in cardiovascular disease, organismal injury, and cancer in mouse liver; (4) The meta-analysis identifies 40 caspase-1 globally regulated genes across tissues, suggesting that caspase-1 globally regulates many novel pathways; and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways. Our findings suggest that caspase-1 regulates many new signaling pathways potentially via its known substrates and also via transcription factors and other proteins that are yet to be identified.
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         Caspase-1
         Microarray datasets
         Meta-analysis
         Inflammation and transcriptome
         Oncology
         Hematology
         Cancer Research
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