Novel Glyceryl Ascorbate Derivatives Inhibit Type 2 Alarmin Cytokine Induction and Promote Expression of Epidermal Barrier Function-Related Factors in Human Keratinocytes in vitro.

INTRODUCTION

Atopic dermatitis is characterized by the interplay among type 2 immune responses, skin barrier dysfunction, and pruritus. Despite the pivotal role of interleukin-33 in the pathogenesis of the disease, novel therapeutic strategies remain limited.

METHODS

In this study, we investigated the effects of 2-O-glyceryl-6-O-hexadecanoyl ascorbic acid (2GA16), assessing its impact on inflammatory cytokine production in an epidermal cell-based atopic dermatitis model. Specifically, 2GA16 was introduced to cultured keratinocytes in an inflammatory state induced by phorbol-12-myristate-13-acetate. The inhibitory effects on inflammatory cytokines were confirmed through gene expression analysis.

RESULTS

The analysis revealed that 2GA16 suppressed the increased expression levels of alarmins, particularly interleukin-33, in a dose-dependent manner (p < 0.01). Epidermal cells treated with 2GA16 exhibited increased expression levels of filaggrin and involucrin, both crucial to epidermal barrier formation (p < 0.05). Such changes were further supported by Western blot analysis and ex vivo tissue staining, which qualitatively showed corresponding changes at the protein level.

CONCLUSION

These findings suggest that 2GA16 may mitigate the symptoms of atopic dermatitis by inhibiting the induction of type 2 alarmin cytokines in keratinocytes and restoring their capacity to form effective epidermal barriers.