Abstract
Background: Benvitimod has been successfully used in the treatment of psoriasis and atopic dermatitis (AD). However, the mechanism remains to be clarified.
Objectives: We aim to assess the effects of benvitimod on MC903-induced dermatitis in mice and to investigate the effects of benvitimod on filaggrin (FLG), involucrin (IVL), and loricrin (LOR) expressions in vivo and in vitro.
Methods: MC903-induced mouse AD model was used to evaluate the effects of benvitimod. Filaggrin, involucrin, and loricrin protein and mRNA expressions in lesions of mice dermatitis were measured by Western blot and quantitative real-time PCR. Normal human epidermal keratinocytes (NHEKs) were cultured. AHR or OVOL1 were knocked down in NHEKs. Then filaggrin, involucrin, and loricrin expressions were measured by Western blot and quantitative real-time PCR.
Results：Topical treatment of benvitimod repaired skin barrier and alleviated skin inflammation in mouse AD model. This effect was inhibited by pretreatment with an AHR antagonist. Benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in lesions of mouse AD model. In addition, benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in NHEKs. Knockdown of AHR or OVO-like (OVOL)1 abrogated the upregulation of filaggrin, involucrin, and loricrin induced by benvitimod.
Conclusions: Benvitimod attenuated MC903-induced mouse dermatitis and upregulated filaggrin, involucrin, and loricrin expressions via AHR-OVOL1 axis.