Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here we define a molecular pathway through which recombinant interleukin-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activates NADPH Oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that anakinra may represent a therapeutic option in addition to its IL-1R1 dependent anti-inflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease. Overall design: mRNA profiles of alveolar macrophages purified from C57BL/6 and Il1r1-/- mice treated or not with Anakinra
Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy.
Specimen part, Genotype, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Prediction of miRNA-mRNA associations in Alzheimer's disease mice using network topology.
Sex, Age, Specimen part
View SamplesWe addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD.
Prediction of miRNA-mRNA associations in Alzheimer's disease mice using network topology.
Sex, Age, Specimen part
View SamplesNeutrophils were isolated form peripheral blood of wildtype and Phd3 null mice, cultured for 4 hours in hypoxia (3% O2) and micro array analysis performed
Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice.
Specimen part, Treatment
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View SamplesWe report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Genetic information, Subject
View Samples