374 Eukaryotic translation initiation factor 4E (eIF4E) as a target of anti-psoriatic treatment

Eukaryotic translation initiation factor 4E (eIF4E) has been known to play a critical role in the regulation of gene expression eukaryotes and affect many essential cellular processes, including proliferation, apoptosis differentiation. We others found eIF4E other eIF subunits upregulated human psoriatic skin thus hypothesized that they are involved pathophysiology psoriasis can serve as direct topical targets for anti-psoriatic treatment. used specific siRNA or briciclib an inhibitor HaCaT cells, 3D-psoriasis tissue model well imiquimod TGFß mouse downregulate protein mRNA itself its two complex partners eIF4A G, eIFs (e.g. eIF1A, eIF2α, eIF3A, eIF3B, eIF5 eIF6). This inhibition abolished inflammation both model, model. Downregulation by application (particularly when given topically) was linked normalization restoration inflammatory milieu epidermal hyperplasia psoriasis, levels pro-inflammatory cytokines TNFα, IL-1b, IL-17 IL-22), keratinocyte differentiation markers KRT16 FLG). These results demonstrate translational imbalance underline crucial played psoriasis. work opens up new avenues development novel treatment strategies targeting and/or eIFs.