Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279586 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Asthmatics have elevated levels of IL-17A compared to healthy controls. IL-17A is likely to contribute to reduced corticosteroid sensitivity of human airway epithelium. Here, we aimed to investigate the mechanistic underpinnings of this reduced sensitivity in more detail. Differentiated primary human airway epithelial cells (hAECs) were exposed to IL-17A in the absence or presence of dexamethasone. Cells were then collected for RNA sequencing analysis or used for barrier function experiments. Mucus was collected for volume measurement and basal medium for cytokine analysis. 2861 genes were differentially expressed by IL-17A (Padj<0.05), of which the majority was not sensitive to dexamethasone (<50% inhibition). IL-17A did inhibit canonical corticosteroid genes, such as HSD11B2 and FKBP5 (p<0.05). Inflammatory and goblet cell metaplasia markers, cytokine secretion and mucus production were all induced by IL-17A, and these effects were not prevented by dexamethasone. Dexamethasone did reverse IL-17A-stimulated epithelial barrier disruption, and this was associated with gene expression changes related to cilia function and development. We conclude that IL-17A induces function-specific corticosteroid-insensitivity. Whereas inflammatory response genes and mucus production in primary hAECs in response to IL-17A were corticosteroid-insensitive, corticosteroids were able to reverse IL-17A-induced epithelial barrier disruption.
2022-10-01 | GSE198683 | GEO
Project description:RNAs were isolated from primary cultures after 24 hour treatment with IL-17A or IL-6 (10 ng/ml) in primary human TBE cells. We used microarrays to analyze the global gene expression profiling of IL-17A or IL-6 regulated genes in TBE cells.
2015-03-28 | GSE67361 | GEO
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis. Cytokine mixture-induced gene expression in primary normal human epidermal keratinocytes (NHEKs) was measured at 24 hours after exposure. NHEKs were exposed to the combination of selected six cytokines (IL-17A: 100 ng/ml, TNF-a: 10 ng/ml, IFN-g: 10 ng/ml, IL-17C: 100 ng/ml, IL-22: 100 ng/ml, IL-36g: 500 ng/ml) , or to the different combinations of five of the six cytokines (in total, 7 different treatments and one untreated control). No replicate experiments were conducted.
2016-03-08 | E-GEOD-77719 | biostudies-arrayexpress
Project description:RNAs were isolated from primary cultures after 24 hour treatment with IL-17A or IL-6 (10 ng/ml) in primary human TBE cells. We used microarrays to analyze the global gene expression profiling of IL-17A or IL-6 regulated genes in TBE cells. TBE cells were grown and stimutaed with the cytokines indicated. Total RNA were then extracted for Affymetrix microarray studies.
2015-03-28 | E-GEOD-67361 | biostudies-arrayexpress
Project description:To understand the overall function of IL-17RD and IL-17RC in IL-17A signaling, RNAseq was performed with WT, Il17rc KO, and Il17rd KO primary mouse keratinocytes following IL-17A treatment along with untreated WT control. Keratinocyte from neonatal WT, Il17rd KO, and Il17rc KO mice were cultured and stimulated with IL-17A (100 ng/mL, PeproTech) for 8h.
2019-04-17 | GSE129176 | GEO
Project description:Expression data from airway brush biopsy samples, differentiated primary cultures of human airway epithelia, CaLu3 cultures at the air liquid interface, and primary cultures of human airway epithelia submerged in nutrient media Organotypic cultures of primary human airway epithelial cells have been used to investigate the morphology, ion and fluid transport, innate immunity, transcytosis, infection, inflammation, signaling, cilia and repair functions of this complex tissue. However, we do not know how close these cultures resemble the epithelia in vivo. In this study, we examine the genome-wide expression profile of human airway epithelial cells in vivo obtained from brush biopsies of the trachea and bronchus of healthy volunteers and compare it to the expression profile of primary cultures of human airway epithelia grown at the air-liquid interface. For comparison we also investigate the expression profile of Calu3 cells grown at the air-liquid interface and primary cultures of human airway epithelia submerged in nutrient media. We compare the transcriptional profile of human in vivo airway epithelia from trachea and bronchus to differentiated primary human airway epithelia cultures, also from trachea and bronchus, and grown at the air-liquid interface. We also included the profile of Calu3 cultures grown at the air-liquid interface and primary cultures submerged in nutrient media.
2010-04-15 | E-GEOD-20502 | biostudies-arrayexpress
Project description:To delineate mechanisms for psoriasis pathogenesis driven by the interleukin-17A, proteomic dysregulations were studied in a Human Primary Keratinocyte model system. Label-free quantification was performed and fold-changes were obtained for abundances of proteins in IL-17A treated keratinocytes versus those from IL-17A treated keratinocytes.
Briefly, Human Primary Keratinocytes were isolated and treated with the cytokine IL-17A (50ng/ml) in incomplete media devoid of any growth factors. Tryptic digested and desalted peptide samples were injected in Thermoscientific Q-Exactive Plus instruments through EasyNLC HPLC autosampler. The instruments were set to MS1 resolution of 70000 and MS2 resolution of 17500. The acquisition experiments were optimized to run on 120 min gradients.
The MS spectra were analyzed using the Thermoscientific mass informatics platform Proteome discoverer version 2.2. The common workflows for discovery proteomics were used with Mascot and SequestHT as search engines.
This dataset helped to simulate the IL-17A-driven inflammation in keratinocytes and uncovered many putative druggable targets in the context of psoriasis.
2022-08-11 | MSV000090116 | MassIVE
Project description:Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals. To evaluate IL-17A-inducible gene transcripts, primary human bronchial ASM cells from 3 mild asthmatic and 3 healthy donors were treated for 2h with IL-17 [10ng/ml] and were probed with the Affymetrix GeneChip array. The 2h time point was carefully chosen in order to identify primary response gene targets and to avoid confounding autocrine mechanisms mediating indirect, or late-phase gene expression responses. Non-stimulated ASM cells from the same patients were used as controls.
2012-02-09 | E-GEOD-35643 | biostudies-arrayexpress
Project description:The goal of the study was to sequence mRNA from tuft cells (identified as CD45-;EpCAM+;IL-25+ using Flare25 reporter mice) in the epithelia of 5 different murine tissues: trachea, thymus, colon, gall baldder, small intestine. As a control, non-tuft epithelial cells (CD45-;EpCAM+;IL-25-) were also isolated. The data were used to identify differentially expressed genes across tuft cells from different tissues and to define a transcriptional tuft cell "signature" that is common to all tissues analyzed but absent in the non-tuft epithelial cells.
2018-05-05 | GSE114067 | GEO
Project description:Objectives. Interleukin-17A (IL-17A) levels are increased in SSc skin and other organs but its role in fibrosis development is highly debated. Since epithelial cells are preferential targets of IL-17A, we aimed at investigating the role of IL-17A in the interactions between epidermis and dermis. Methods. Organotypic cultures of HD full human skin were challenged with IL-17A,TNF and TGF-β. Inflammatory mediators and type I collagen (col-I) levels were quantified. IL-17A- and TGF-β-induced changes in gene expression in full human skin were analysed by RNA sequencing. Results. In full human skin, TGF-β induced pro-fibrotic gene signature dominated by Wnt signalling. While IL-17A strongly promoted expression of many pro-inflammatory genes, it did not affect collagen gene levels but decreased Wnt signalling. At the protein level, IL-17A showed direct anti-fibrotic effects, as well as decreased by 2-fold TGF-β-triggered col-I production. Conclusions. We report here firstly, a novel model of fibrotic skin and secondly, that IL-17A acts as a potent anti-fibrotic factor in the full human skin. Furthermore, we show that IL-17A not only decreased ECM deposition by itself, but also counteracted TGF-β pro-fibrotic activities. Thus, IL-17A seems to play a dual role in SSc skin – strongly pro-inflammatory but anti-fibrotic, being an example that fibrosis and inflammation, although closely related, are two different processes. These data may help in directing and interpreting therapeutic approaches in SSc, since both, IL-17A and TGF-β, are target candidates in clinical trials.
2020-02-11 | GSE122305 | GEO