Oxidative injury and inflammation have been implicated in the genesis of hypertension but the mechanisms involved are not fully understood. We describe a new pathway in which angiotensin II promotes dendritic cell (DC) activation of T cells and ultimately hypertension. NADPH oxidase-dependent superoxide production is increased 5-fold in DCs isolated from hypertensive mice as compared to sham-treated mice. This is associated with DC accumulation of protein-isoketal adducts and production of IL-6, IL-1 and IL-23. DCs from hypertensive mice but not sham mice promote survival and proliferation of CD8+ T cells in culture. Chemically diverse isoketal scavengers not only prevent activation and immunogenicity of DCs, but also attenuate angiotensin II-induced hypertension. Moreover, adaptive transfer of DCs from hypertensive mice prime development of hypertension in response to a subpressor dose of angiotensin II. Exposure of DCs to tert butyl hypdroperoxide promoted isoketal formation, DC stimulation of CD8+ T cell proliferation and primed hypertension in response to low dose angiotensin II. Serum isoprostanes, precursors to isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension. These studies show that angiotensin II-induced hypertension activates DCs, in large part by causing superoxide production and formation of isoketals. They define a new mechanism of hypertension and identify a potential new therapeutic approach for this disease.
DC isoketal-modified proteins activate T cells and promote hypertension.
Age, Specimen part
View SamplesWe describe here a male infant with a 100 kb de novo Xq28 deletion encompassing parts of the TMEM187 and MECP2 protein-coding genes and the IRAK1 protein-coding gene, as well as the MIR3202-1, MIR3202-2, and MIR718 RNA-coding genes. We analyzed the impact of human IRAK-1 deficiency on a genome-wide gene expression in human fibroblasts in response to TLR2/6, TLR4 agonists as well as to IL-1 and TNF-, using primary fibroblasts from healthy controls and IRAK-4-, MyD88- and MECP2-deficient patients for comparison.
Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.
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View SamplesHydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that <3,500 Da HWP is safe for use in cosmetics, it remains biologically unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulating signaling by HWP is poorly understood.
An acid-hydrolyzed wheat protein activates the inflammatory and NF-κB pathways leading to long TSLP transcription in human keratinocytes.
Specimen part, Treatment
View SamplesGene expressions relate to the pathogenesis of periodontitis and have a crucial role in local tissue destruction and susceptibility to the disease. The aims of the present study were to explore comprehensive gene expressions/transcriptomes in periodontitis-affected gingival tissues, and to identify specific biological processes.
Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues.
Sex, Specimen part
View SamplesMED1 (Mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific MED1-null (MED1epi-/-) mice using the K5Cre-LoxP system.
Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling.
Specimen part
View SamplesGene expression was examined in granulosa cells and oocytes in various stage of follicle and in vitro grown oocytes and granulosa cells complexes in sus scrofa.
Gene expression patterns in granulosa cells and oocytes at various stages of follicle development as well as in in vitro grown oocyte-and-granulosa cell complexes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β.
Specimen part, Disease, Disease stage, Treatment, Time
View SamplesTo investigate the time-dependent and coordinated sequence of inflammation-related events, and the dynamic features of macrophage polarisation/activation, we build and validated an in vitro model based on primary human monocytes
Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.
Specimen part
View SamplesWe generated h-hepatocyte chimeric mice with livers that were predominantly repopulated with h-hepatocytes in a h-growth hormone (GH)-deficient state. Using microarray profiles, comparison between h-hepatocytes from h-GH-treated and untreated mice identified 14 GH-up-regulated and four GH-down-regulated genes, including IGF-1, SOCS2, NNMT, IGFLS, P4AH1, SLC16A1, and SRD5A1, and FADS1 and AKR1B10, respectively.
Growth hormone-dependent pathogenesis of human hepatic steatosis in a novel mouse model bearing a human hepatocyte-repopulated liver.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.
Specimen part, Cell line, Treatment
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