Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis


ABSTRACT: We sought to provide a comprehensive evaluation of the effects of TNF-α and IL-17 on the keratinocyte gene profile in order to identify genes that might be co-regulated by these cytokines. We then sought to determine how genes that were synergistically activated by both cytokines relate to the psoriasis transcriptome. Here, we identified 160 unique genes that were synergistically up-regulated by IL-17 and TNF-α and 188 unique genes where the two cytokines had at least an additive effect. Among highly up-regulated genes were those involved in neutrophil and lymphocyte chemotaxis, inflammation, and epidermal differentiation. Synergistically up-regulated genes included some of the highest expressed genes in lesional psoriatic skin with an impressive correlation between IL-17/TNF-α induced genes and the psoriasis gene signature. In conclusion, keratinocytes may be key drivers of pathogenetic inflammatory circuits in psoriasis through integrating responses to TNF-α and IL-17. This may explain high efficacy of targeting psoriasis with either anti-TNF-α or agents that block Th17 T-cells/IL-17 and has important implications for the development of new therapeutic agents. Comparison of keratinocyte responses to IL-17, TNF-α (1 ng mL-1 and 10 ng mL-1), and the combination of both cytokines in psoriasis.

ORGANISM(S): Homo sapiens

SUBMITTER: Mayte Suarez-Farinas 

PROVIDER: E-GEOD-24767 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis.

Chiricozzi Andrea A   Guttman-Yassky Emma E   Suárez-Fariñas Mayte M   Nograles Kristine E KE   Tian Suyan S   Cardinale Irma I   Chimenti Sergio S   Krueger James G JG  

The Journal of investigative dermatology 20101118 3


Psoriasis is a complex inflammatory disease mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations, e.g., IL-17, IL-22, and IFN-γ. The mechanisms by which innate and adaptive immune cytokines regulate inflammation in psoriasis are not completely understood. We sought to investigate the effects of TNF-α and IL-17 on keratinocyte (KC) gene profile, to identify genes that might be coregulated by these cytokines and determine how synergistically activated  ...[more]

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