Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from keratinocytes treated either with IL-22 or combination of tofacitinib (JAK1/3 inhibitor) and IL-22 at 6 hours

ABSTRACT: JAK inhibitors like tofacitinib were thought to act primarily on T cells. However, our data and recent research suggest that JAK receptors are also present on keratinocytes. Here, we show effect of tofacitinib on primary keratinocytes, which could explain effects of topical tofacitinib treatment in psoriasis. We have performed whole transcriptome analysis (using microarray) on RNA isolated from cultured primary keratinocytes treated either with IL-22 alone or combination of tofacitinb and IL-22 at 6 hours

ORGANISM(S): Homo sapiens

PROVIDER: GSE104509 | GEO | 2017/10/03

SECONDARY ACCESSION(S): PRJNA412876

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from keratinocytes treated either with IL-22 or combination of tofacitinib (JAK1/3 inhibitor) and IL-22 at 6 hours

Project description:Expression data from keratinocytes treated either with IL-22 or combination of tofacitinib (JAK1/3 inhibitor) and IL-22 at 6 hours

| PRJNA412876 | ENA

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

2018-10-24 | PXD006581 | Pride

Gene expression profile of human epidermal keratinocytes in response to IFNgamma, IL-4, IL-6, IL-17A and IL-22

Project description:To understand the role of epidermal keratinocytes in immunopathology of skin diseases with predominant T helper (Th) cell responses, we measured the genome-wide transcriptional profile of human keratinocytes in response to IFNgamma, IL-4, IL-17A or IL-22, major cytokines produced by Th1, Th2, Th17 or Th22 cells, respectively. IL-6 was also included in the transcriptional profile analysis because a variety of pro-inflammatory stimuli stimulate human keratinocytes to produce IL-6 that has an autocrine or paracrine role in epidermal immunity. We aimed to discover commonly expressed genes in human keratinocytes in response to pro-inflammatory cytokines, which would be associated with common pathophysiological responses in various skin diseases such as skin permeability barrier disruption or epidermal hyperplasia. Normal human keratinocytes (NHKs) were stimulated with IFNγ, IL-4, IL-6, IL-17A and IL-22 for 24 hours and harvested for total RNA extraction and hybridization on Affymetrix microarrays.

2014-10-02 | E-GEOD-53751 | biostudies-arrayexpress

Pathologic Immune Pathways in Psoriasis are Rapidly Attenuated by Tofacitinib Treatment: A Randomized Phase 2 Study in Patients with Moderate to Severe Psoriasis

Project description:Here we elucidate the molecular mechanism of tofacitinib, an oral Janus kinase inhibitor, in psoriasis. Tofacitinib exhibits a multi-tiered action, with early direct effects on keratinocytes and histological and transcriptomic improvement prior to IL-17 reduction. Twelve patients with plaque psoriasis were randomized (3:1) to receive tofacitinib 10Â mg or placebo twice daily for 12 weeks. Biopsies were taken from lesional and nonâlesional skin at baseline, and from lesional skin on Day 1, Day 3, and Weeks 1, 2, 4 and 12. Biopsies were examined for psoriatic epidermal features (thickness; Ki67+ keratinocytes, keratin 16 [KRT16] mRNA expression; phosphoSTAT [pSTAT] + nuclei) and T-cell and dendritic cell (DC) subsets using immunohistochemistry. mRNA transcripts were quantified by microarray.

2016-06-30 | E-GEOD-69967 | biostudies-arrayexpress

Gene expression profile of human epidermal keratinocytes in response to IFNgamma, IL-4, IL-6, IL-17A and IL-22

2014-10-02 | GSE53751 | GEO

Primary Human Bronchial Epithelial Cells (HBEs) Stimulated with IL-22 and IL-17

2008-01-23 | GSE10240 | GEO

Transcription profiling of primary human bronchial epithelial cells stimulated with IL-22 and IL-17

Project description:Primary HBE cells were stimulated with IL-22 and IL-17, and gene expression was studied using an Affymetrix platform microarray, in order to investigate which genes may be upregulated or downregulated in response to these cytokines. Of particular interest was the host defense genes such as antimicrobial peptides, which have been shown to be upregulated by IL-22 and IL-17 in skin keratinocytes. Experiment Overall Design: There were 4 conditions to this study (media, IL-22, IL-17 and IL-22+17) and there were 3 biological replicates of each condition. Experiment Overall Design: Gene expression study using one timepoint of 24 hours after stimulating these primary cells with the above conditions

2008-06-11 | E-GEOD-10240 | biostudies-arrayexpress

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

Project description:The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

2017-05-26 | GSE99293 | GEO

Fezakinumab (anti-IL-22) treatment in adults with moderate-to-severe atopic dermatitis

Project description:We conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD unresponsive to conventional topical or systemic treatment. Fezakinumab (ILV-094; anti IL-22 monoclonal antibody) monotherapy was administered for 12 weeks (primary endpoint), and clinical responses were followed until week 20. AD transcriptome significantly improved at week 12 in fezakinumab vs. placebo (p<1E-18).

2018-09-17 | GSE99802 | GEO

Transcription profiling of human primary keratinocytes treated with either IL-17, IL-22 or IFNg

Project description:In this study, we shought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Experiment Overall Design: In this study, primary keratinocytes were treated with either IL-17, IL-22 or IFNg for 24 hours then harvested for RNA extraction and subsequent gene array analysis

2008-10-24 | E-GEOD-12109 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data