Altered expression of S100 fused-type proteins in an atopic dermatitis skin model.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with elevated interleukin (IL)-4 and IL-13 signatures and extensive barrier dysfunction, which is correlated with the downregulation of filaggrin (FLG). FLG is a member of the S100 fused-type protein family and this family also includes cornulin (CRNN), filaggrin-2 (FLG2), hornerin (HRNR) repetin (RPTN), trichohyalin (TCHH) and trichohyalin-like 1 (TCHHL1). The present study aimed to examine the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins using a three-dimensional (3D) AD skin model by immunohistochemical study and quantitative polymerase chain reaction. In the 3D AD skin model, which was generated by a stimulation of recombinant IL-4 and IL-13, the expression of FLG, FLG2, HRNR and TCHH was decreased, while that of RPTN was increased in comparison to the 3D control skin. In the FLG knockdown (KD) 3D skin model, which was generated using FLG siRNA, the expression of HRNR was increased. The expression of the other proteins did not differ to a statistically significant extent. The expression of fused-S100 type protein family members may differ in AD skin. This suggests that these proteins play different roles in the pathogenesis of AD.