Effect of tumour necrotic factor-α, interleukin-17 and interleukin-22 on the expression of filaggerin-2 and hornerin: Analysis of a three-dimensional psoriatic skin model.

Abstract

Background: Filaggrin-2 (FLG2) and hornerin (HRNR) are members of the S100 fused-type protein family, which share many properties with filaggrin (FLG). A previous study demonstrated that the expression of FLG2 was significantly decreased in psoriatic skin relative to that in normal skin. In contrast, the HRNR expression in psoriatic skin varied among studies.

Objectives: We aimed to investigate the effect of tumour necrosis factor-α (TNF-α), IL-17A and IL-22 on the expression of FLG2 and HRNR using a three-dimensional psoriatic skin model.

Methods: In the present study, we generated a 3D psoriatic skin model that was stimulated with TNF-α, IL-17A and IL-22 for 3D skin equivalents. Using this model, we examined the altered expression of FLG2 and HRNR by quantitative reverse transcription polymerase chain reaction and immunostaining.

Results: In the 3D psoriatic skin model, the expression of FLG2 and HRNR was significantly reduced compared with that in the 3D control skin. FLG2 expression was significantly decreased by stimulation with TNF-α, IL-17A and IL-22. In contrast, the expression of HRNR was markedly increased by stimulation with IL-22, although it was slightly decreased by TNF-α or IL-17A compared to the 3D control skin.

Conclusion: TNF-α, IL-17A and IL-22 have different effects on FLG2 and HRNR expression and epidermal structure formation. Furthermore, FLG2 and HRNR may play different roles in barrier formation and the pathogenesis of psoriasis.