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SHR Neuro Cancer Cardio Lipid Metab Microb

Golob-Schwarzl, N; Pilic, J; Benezeder, T; Bordag, N; Painsi, C; Wolf, P.
Eukaryotic Initiation Factor 4E (eIF4E) as a Target of Anti-Psoriatic Treatment.
J Invest Dermatol. 2024; 144(3):500-508.e3 Doi: 10.1016/j.jid.2022.12.028
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Leading authors Med Uni Graz

Golob-Schwarzl Nicole

Wolf Peter

Co-authors Med Uni Graz

Benezeder Theresa Helena

Bordag Natalie

Painsi Clemens

Pilic Johannes

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Abstract:

Eukaryotic initiation factor 4E (eIF4E) has been known to play a critical role in the regulation of gene expression and essential cellular processes, such as proliferation, apoptosis and differentiation. In this study, we explored its role in the pathophysiology of psoriasis. The inhibition of eIF4E by small interfering RNA or briciclib, an eIF4E small molecule inhibitor, downregulated the expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (eg, eIF1A, eIF2α, eIF3A, eIF3B, eIF5, and eIF6). This inhibition also abolished psoriatic inflammation in both the imiquimod and TGFß mouse model, as well as in a human 3 dimensional-psoriasis tissue model. Downregulation of eIF4E and the other eIFs by application of briciclib (particularly when given topically) was linked to the normalization of cellular proliferation, epidermal hyperplasia, levels of proinflammatory cytokines (eg, TNFα, IL-1b, IL-17, and IL-22), and keratinocyte differentiation markers (eg, KRT16 and FLG). These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up avenues for the development of novel topical antipsoriatic treatment strategies by targeting eIF4E.

Find related publications in this database (using NLM MeSH Indexing)

Animals - administration & dosage

Mice - administration & dosage

Humans - administration & dosage

Eukaryotic Initiation Factor-4E - genetics

RNA, Small Interfering - genetics, metabolism

Protein Processing, Post-Translational - administration & dosage

Psoriasis - drug therapy

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