NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE77719 Query DataSets for GSE77719
Status Public on Mar 08, 2016
Title IL-17A plays a central role in the expression of psoriasis signature genes through induction of IkappaB-zeta in keratinocytes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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.
 
Contributor(s) Muromoto R, Hirao T
Citation(s) 26944069
Submission date Feb 09, 2016
Last update date Jun 30, 2017
Contact name Ryuta Muromoto
E-mail(s) muro@pharm.hokudai.ac.jp
Organization name Hokkaido University
Department Faculty of Pharmaceutical Sciences
Street address Kita 12 Nishi 6, Kita-ku
City Sapporo
State/province Hokkaido
ZIP/Postal code 060-0812
Country Japan
 
Platforms (1)
GPL10332 Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Feature Number version)
Samples (8)
GSM2057818 NHEK_unstimulated_24h_rep1
GSM2057819 NHEK_6-cytokine-stimulated_24h_rep1
GSM2057820 NHEK_5-cytokine(lacking IL-17A)-stimulated_24h_rep1
Relations
BioProject PRJNA311287

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77719_RAW.tar 80.6 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.