TNF-α Downregulates Filaggrin and Loricrin through c-Jun N-terminal Kinase: Role for TNF-α Antagonists to Improve Skin Barrier

Filaggrin (FLG), loricrin (LOR), and involucrin are important epidermal barrier proteins. As psoriasis is characterized by overexpression of tumor necrosis factor-alpha (TNF-alpha) and impaired skin barrier, we investigated the expression of skin barrier proteins in psoriasis patients and whether their expression was modulated by TNF-alpha. The expression of FLG and LOR was found to be decreased in lesional and non-lesional skin of psoriasis patients. A correlation was found between the expression of TNF-alpha and epidermal barrier proteins in psoriasis. TNF-alpha was found to modulate the expression of FLG and LOR via a c-Jun N-terminal kinase-dependent pathway. Importantly, we report that clinical treatment of psoriasis patients with a TNF-alpha antagonist results in significant enhancement of epidermal barrier protein expression. Our current study suggests that TNF inhibits barrier protein expression, and TNF-alpha antagonists may contribute to clinical improvement in patients with psoriasis by improving barrier protein expression.