IL-17A and IL-6 -stimulated expression data from primary epithelial cell cultures derived from human trachea tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Reen Wu
PROVIDER: E-GEOD-67361 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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:Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here, we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C (IL-17RC) to mediate its stability, posttranslational modification, and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17 receptor signaling complex. Accordingly, CMTM4-deficient mice were largely resistant to experimental psoriasis. Collectively, our data identified CMTM4 as an essential component of the IL-17 receptor and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
2022-12-02 | PXD036366 | Pride
Project description:Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. Interleukin-17A is a pro-inflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. 26-weeks old apolipoprotein E-deficient (Apoe-/-) mice were fed a standard chow diet and treated either with IL-17A mAb (n=15) or irrelevant immunoglobulin (n=10) for 16 weeks. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (P=0.001) by reducing inflammatory burden and cellular infiltration (P=0.01) and improved lesion stability (P=0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, sensitization of antigen-presenting cells toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a pro-inflammatory milieu and up-regulation of molecules expressed by the IL-17A-induced macrophage subtype. We here show for the first time that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in Apoe-/- mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte / macrophage lineage. In addition, translational experiments underline the relevance for the human system. Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).
2014-10-01 | E-GEOD-60824 | biostudies-arrayexpress
Project description:Global kinase activity induced by cytokines IL-32g and IL-17A/F were determined using peptide arrays representing phophorylation targets The objective of this study was to identify common and unique phosphorylation targets of pro-inflammatory cytokines IL-32 and IL-17. These cytokines are associated with the pathogenesis and severity of chronic inflammatory disorders, therefore signaling intermediates of these cytokines could be beneficial as alternate theraputic targets that may likely influence different inflammatory pathways. Phosphorylation of proteins is a critical mechanism in the regulation of cellular processes. This process is meticulously regulated by enzymes known as kinases, which are increasingly being identified as drug targets for a variety of diseases. In this study we interrogated kinase activities (kinome) induced in the presence of the human recombinant cytokines IL-32g and IL-17A/F employing peptide arrays representing 300 peptides, printed in triplicate, representing select phosphorylation events. Human macrophage-like THP-1 cells were used for this comparative kinome analysis. Macrophage-like THP-1 cells were stimulated with either IL-32g (20 ng/ml) or IL-17A/F (20 ng/ml) for 15 min, and the peptide arrays were used to comprehensively analyze protein phosphorylation profiles in the presence of these cytokines. Two independet biological experiments were performed and the kinoem analysis was done in triplicates for each. The phosphorylations of the peptides on the array were quantified in the cytokine-treated cells relative to the un-stimulated control cells. Differentially phosphorylated targets were defined as greater than 1.5 fold increase or decrease (p < 0.06) in phosphorylation compared to un-stimulated control cells.
2011-04-16 | E-GEOD-28649 | biostudies-arrayexpress
Project description:IL-17A is a pro-inflammatory cytokine that promotes host defense against infections and contributes to the pathogenesis of chronic inflammatory diseases. Dendritic cells (DC) are antigen-presenting cells responsible for adaptive immune responses. Here, we report that IL-17A induces intense remodeling of lipid metabolism in human monocyte-derived DC, as revealed by microarrays analysis. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases. We used microarrays analysis to understand the impact of IL-17A on human monocyte-derived human dendritic cells. We found overexpression of many genes involved in lipid metabolism in IL-17A-treated dendritic cells compared to untreated dendritic cells. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases. RNA was extracted from untreated in vitro-generated DC at day 0 (DC, 4 biological replicates ) or DC cultured for 12 days with IL-17A, in the absence or presence of IFN-g (DC-17 and DC-G17, 5 biological replicates)
2015-03-31 | E-GEOD-53163 | biostudies-arrayexpress
Project description:Psoriatic arthritis is a seronegative polyarticular form of inflammatory arthritis . Genetic analysis implicates a role for both IL-17/23 axis and CD8+ T cells in disease susceptibility. Using RNA-seq we identified differential gene expression between synovial IL-17A+(IFNy+/-) CD8+ T cells compared to IL-17A-IFNy+ CD8+ T cells and IL-17A+CD4+ T cells from the synovial fluid of psoriatic arthritis patients. We find that IL-17A+CD8+ T cells have a transcriptional overlap with IL-17A+CD4+ T cells. Overall we show these IL-17A+ CD8+ T cells have a polyfunctional, pro-inflammatory capacity and are potentially derived from common precursors, shared with IL-17A-CD8+ T cells.
2020-04-17 | GSE137510 | GEO
Project description:The goal of this study was to elucidate the effects of inflammation on bone metabolism. As we found IL-17A is induced immediately after bone injury and Il17aâ/â mice showed delayed healing, we analyzed the effects of IL-17A on mesenchymal cells in the repair tissue. Most of the IL-17RA+ cells were PαS cells. We collected these cells and analyzed their response to IL-17A by RNA sequencing. This analysis will provide a mechanistic insight into the mechanism of how IL-17A promote bone formation in the context of bone fracture healing. PαS cells were harvested from the injury tissue of wild-type mice and cultured with or without IL-17A or BMP-2. RNAs were harvested at day 7.
2016-03-08 | E-GEOD-77172 | biostudies-arrayexpress
Project description:IL-17A has emerged as a pivotal driver of tissue pathology in many immune-mediated inflammatory diseases. Despite sharing 50% sequence homology and the same signalling pathway, the role of IL-17F remains less clear. RNA sequencing of human IL-17 popualtions isolated using a cytokine capture technique identified clear transcriptional differences in IL-17A and IL-17F producing cells, with IL-17A producing cells showing enrichment for cytokine signaling and IL-17F producing cells showing enrichment for cellular replication.
2023-11-20 | GSE189230 | GEO
Project description:Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in clinical trials. Although inhibition of these cytokines is effective for treating psoriasis, IL-12/23 inhibition attenuates Crohn's disease, while IL-17A or IL-17RA inhibition exacerbates disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the mdr1a- /- mouse model of colitis. IL-23 inhibition attenuated disease by decreasing colonic inflammation while enhancing Treg accumulation. Exacerbation of colitis by IL-17A or IL-17RA inhibition was associated with severe weakening of the intestinal epithelial barrier, culminating in increased colonic inflammation and accelerated mortality. These data show that IL-17A acts on intestinal epithelium to promote barrier function and provides insight into mechanisms underlying exacerbation of Crohn's disease when IL-17A or IL-17RA is inhibited.
2015-08-20 | GSE72212 | GEO
Project description:Molecular profiling of effect of TNFα neutralization in contrast to anti-IL-17A or anti-IL-17F treatment for 28 days in lungs of M. tuberculosis infected C57BL/6 mice. Animals were treated once per week (starting day-1) with anti-mouse IL-17A or IL-17F antibodies (20 mg/kg i.p.), anti-mouse TNFα antibody (10 mg/kg), respective isotype control antibodies. Moreover, infected and non-infected TNFα-deficient mice were also analysed. Gene expression data revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection (including host-pathogen interactions, macrophage recruitment, activation and polarization, host-anti-mycobacterial activities, immunomodulatory responses and extracellular matrix metallopeptidases) after TNFα blockade, while IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after M. tuberculosis infection.
2016-12-02 | E-MTAB-5218 | biostudies-arrayexpress