TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier.
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| 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.
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| Authors | Byung Eui Kim, Michael D Howell, Emma Guttman-Yassky, Emma Guttman, Patricia M Gilleaudeau, Irma R Cardinale, Mark Boguniewicz, James G Krueger, Donald Y M Leung |
| Journal | The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 6 Pg. 1272-9 (Jun 2011) ISSN: 1523-1747 [Electronic] United States |
| PMID | 21346775 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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