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- Title
TNF-α Downregulates Filaggrin and Loricrin through c-Jun N-terminal Kinase: Role for TNF-α Antagonists to Improve Skin Barrier.
- Authors
Kim, Byung Eui; Howell, Michael D.; Guttman, Emma; Gilleaudeau, Patricia M.; Cardinale, Irma R.; Boguniewicz, Mark; Krueger, James G.; Leung, Donald Y. M.
- Abstract
Filaggrin (FLG), loricrin (LOR), and involucrin are important epidermal barrier proteins. As psoriasis is characterized by overexpression of tumor necrosis factor-α (TNF-α) and impaired skin barrier, we investigated the expression of skin barrier proteins in psoriasis patients and whether their expression was modulated by TNF-α. 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-α and epidermal barrier proteins in psoriasis. TNF-α 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-α antagonist results in significant enhancement of epidermal barrier protein expression. Our current study suggests that TNF inhibits barrier protein expression, and TNF-α antagonists may contribute to clinical improvement in patients with psoriasis by improving barrier protein expression.
- Subjects
SKIN diseases; TUMOR necrosis factors; PSORIASIS; EPIDERMAL diseases; PROTEIN kinases; PATIENTS
- Publication
Journal of Investigative Dermatology, 2011, Vol 131, Issue 6, p1272
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2011.24