Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

ABSTRACT: c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of imiquimod-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced imiquimod-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed a reduced imiquimod-induced acanthosis and keratinocytes proliferation despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced imiquimod-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE164580 | GEO | 2021/01/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

Project description:c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of imiquimod-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced imiquimod-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed a reduced imiquimod-induced acanthosis and keratinocytes proliferation despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced imiquimod-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.

2021-01-12 | GSE164579 | GEO

Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation [Affymetrix]

Project description:Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Total RNA obtained from skin explants taken from AhR heterozygous or knock-out mice treated pericutaneously with imiquimod for 0 and 2d.

2014-06-11 | E-GEOD-47607 | biostudies-arrayexpress

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation

| PRJNA691238 | ENA

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

| PRJNA691245 | ENA

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

| PRJNA691246 | ENA

Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation [RNA-Seq]

Project description:Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist

2014-06-11 | E-GEOD-47944 | biostudies-arrayexpress

C10orf99/GPR15L Regulates Proinflammatory Response of Keratinocytes and Barrier Formation of the Skin

Project description:The epidermis, outermost layer of the skin, forms a barrier and is involved in innate and adaptive immunity in an organism. Keratinocytes participate in all these three protective processes. However, a regulator of keratinocyte protective responses against external dangers and stresses remains elusive. We found that upregulation of the orphan gene 2610528A11Rik was a common factor in the skin of mice with several types of inflammation. In the human epidermis, peptide expression of G protein-coupled receptor 15 ligand (GPR15L), encoded by the human ortholog C10orf99, was highly induced in the lesional skin of patients with atopic dermatitis or psoriasis. C10orf99 gene transfection into normal human epidermal keratinocytes (NHEKs) induced the expression of inflammatory mediators and reduced the expression of barrier-related genes. Gene ontology analyses showed its association with translation, mitogen-activated protein kinase (MAPK), mitochondria, and lipid metabolism. Treatment with GPR15L reduced the expression levels of filaggrin and loricrin in human keratinocyte 3D cultures. Instead, their expression levels in mouse primary cultured keratinocytes did not show significant differences between the wild-type and 2610528A11Rik deficient keratinocytes. Lipopolysaccharide-induced expression of Il1b and Il6 was less in 2610528A11Rik deficient mouse keratinocytes than in wild-type, and imiquimod-induced psoriatic dermatitis was blunted in 2610528A11Rik deficient mice. Furthermore, repetitive subcutaneous injection of GPR15L in mouse ears induced skin inflammation in a dose-dependent manner. These results suggest that C10orf99/GPR15L is a primary inducible regulator that reduces the barrier formation and induces the inflammatory response of keratinocytes.

2022-02-28 | GSE189751 | GEO

JNK1 Ablation in Mice Confers Long-term Metabolic Protection from Diet-Induced Obesity at the Cost of Increased Skin Oxidative Damage

Project description:Obesity and insulin resistance are associated with oxidative stress, which may be implicated in their progression. The kinase JNK1 emerged as a promising drug target for the treatment of obesity and type-2 diabetes. However, JNK1 is a key mediator of the oxidative stress response, promoting either cell dead or survival depending on magnitude and context of its activation. Furthermore, JNK inactivation shortens lifespan in drosophila and c. elegans. To learn on the safety and efficacy of long-term JNK inhibition in vertebrates, we investigated mice lacking JNK1 (JNK1-/-) exposed over a long period to an obesogenic high-fat diet (HFD). JNK1-/- mice chronically fed an HFD developed more skin oxidative damage because of reduced catalase expression, but also showed sustained protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, paralleled by decreased oxidative damage in fat and liver. We conclude that JNK1 is a relatively safe drug target for obesity-related diseases. RNA was collected from liver, skin and epididymal fat tissues from JNK1 KO mice and WT mice fed in high fat diet. Each condition was run in quadruplicate

2016-09-01 | E-GEOD-73759 | biostudies-arrayexpress

Next Generation Sequencing of wild type (WT) and K14 conditional Il9ra-/- mice ear epidermal cell layers

Project description:Complex interactions of keratinocytes with various cells like inflammatory cells and stromal cells contribute to the pathogenesis of chronic inflammatory dermatoses. In proinflammatory cytokines mediating such ill settings, interleukin (IL)-9 plays a pathological role in inflammatory dermatoses. However, IL-9-related mechanisms in such diseases are still incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9 receptor alpha-chain-deficient mice (K14CRE/ERTIl9ra∆/∆ mice) to examine the role of IL-9 in multicellular interactions under the condition of chronic skin inflammation. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9ra∆/∆ mice significantly reduced the severity of dermatitis and mast cell infiltration compared to K14WTIl9rafl/fl mice as controls. The transcriptome analyses of psoriasis-like lesions showed that the level of peptide tyrosine-tyrosine (Pyy), a member of neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9ra∆/∆ epidermis. Blockade of Pyy suppressed thickening of the epidermis and mast cell number in imiquimod-treated wild-type mice. Together with in vitro studies indicating a capacity of Pyy to induce IL-9 production and chemotactic activity of bone marrow-derived mast cells (BMMCs), these suggest that Pyy-mediated interplay of keratinocytes and mast cells induces psoriasiform inflammation. Further investigation focusing on the IL-9-Pyy axis would provide a new modality for treatment of chronic inflammatory dermatoses.

2022-08-09 | GSE190867 | GEO

TLR7-dependent eosinophil degranulation links psoriatic skin inflammation to small-intestinal inflammatory changes

Project description:Increased intestinal permeability can exacerbate psoriasis, a systemic inflammatory disease with complex pathogenesis. Using a mouse model of psoriasis elicited by the TLR7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by small-intestinal inflammatory changes associated with eosinophil degranulation which led to impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were accelerated in mice that are prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells treated with media containing eosinophil granule proteins exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal inflammatory changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by eosinophil transfer. Imiquimod levels and eosinophil distribution were positively correlated in the intestine. TLR7-deficient mice did not show intestinal eosinophil degranulation and exhibited attenuated skin and small-intestinal inflammation following imiquimod application. These results suggest a TLR7-dependent bidirectional skin-to-gut communication in psoriatic inflammation, and that intestinal inflammatory changes can accelerate psoriasis.

2024-04-30 | GSE237610 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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