RNA Seq analysis of the response of fisetin and rapamycin treatment on TNFα plus IL17A-stimulated primary human keratinocytes

Chronic autoimmune skin disease characterized by epidermal proliferation with hyper- and para-keratosis. The aberrant background immune response involves helper T-lymphocyte types 1 and 17 and their respective secreted cytokines tumor necrosis factor alpha (TNF) and interleukin 17 (IL-17). These pro-inflammatory cytokines stimulate the activation of keratinocytes, resulting in the release of acute phase cytokines, followed by chronic phase cytokines thus promotes induced hyperplasia of keratinocyte. The pro-differentiative action of fisetin on dual cytokine-induced abnormally proliferating keratinocyte revealed downregulation of psoriasis-associated genes and activation of autophagic genes, as well as normalization of genes involved in keratinocyte terminal differentiation. These result supports the effect of fisetin on improving psoriasis like inflammatory flareups in cultured keratinocyte in vitro. Monolayer of primary adult Human epidermal keratinocyte were stimulated with dual cytokine TNFα (10ng/mL) and IL-17A (20ng/mL) for 24h. Cells were treated with Fisetin and Rapamycin for their particular concentration. Control group of cells were maintained in their growth medium (Primary keratinocyte growth medium: 1% Human Keratinocyte Growth Factor (HKGS) and 1% Penicillin Streptomycin (PEST) containing EpiLife Medium).