Role of IL-33 in modulating filaggrin and acid ceramidase expression for epidermal barrier restoration after tape stripping in mice

Summary: Abstract Body: Preserving the epidermal barrier is vital for healthy skin. The stratum corneum depends on ceramides, with ASAH1b being significant due to its link with increased sphingomyelin deacylase activity in atopic dermatitis (AD). Elevated interleukin-33 (IL-33) levels in mice mimic AD-like skin conditions. This study explored IL-33's role in epidermal barrier function using tape stripping to induce skin damage in wild-type (WT) and IL-33 knockout (IL-33KO) mice. Trans-epidermal water loss (TEWL) was monitored over 72 hours, and skin samples were analyzed through tissue staining, immunohistochemistry (IHC), and real-time PCR. Additionally, cultured Ker-CT cells were treated with IL-33 and TNF-α to examine their effects on ASAH1b expression, including experiments with IL-33 knockdown. Tape stripping increased TEWL similarly in WT and IL-33KO mice. However, IL-33KO mice displayed thicker epidermis and a more pronounced granular layer compared to WT mice. IHC analysis showed elevated filaggrin (FLG) protein expression in both groups, with IL-33KO mice showing a greater increase. Tape stripping induced TSLP mRNA expression in WT mice but not IL-33KO mice. Additionally, acid ceramidase (ASAH1 and ASAH1b) expression at protein and mRNA levels was significantly upregulated in WT mice but not in IL-33KO mice after tape stripping. In Ker-CT cells, IL-33 treatment induced ASAH1b mRNA expression in a time- and concentration-dependent manner. TNF-α treatment increased ASAH1b mRNA expression in IL-33-knockdown cells at 16 hours but not 24 hours, while it maintained expression at both time points in WT cells, suggesting IL-33 helps sustain ASAH1b mRNA levels. This study highlights IL-33's critical role in promoting filaggrin and acid ceramidase expression following epidermal barrier disruption, despite no direct effect on TEWL. These findings offer new insights into IL-33's regulatory role in skin barrier maintenance and its implications in atopic dermatitis. Md Razib Hossain¹, Tuba M. Ansary¹, Mayumi Komine¹, Mamitaro Ohtsuki¹ 1. Dermatology, Jichi Ika Daigaku, Shimotsuke, Tochigi Prefecture, Japan. Epidermal Structure and Barrier Function