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

被引：168

作者：

Kim, Byung Eui ^{[1
]}

Howell, Michael D. ^{[1
,2
]}

Guttman, Emma ^{[3
,4
]}

Gilleaudeau, Patricia M. ^{[3
]}

Cardinale, Irma R. ^{[3
]}

Boguniewicz, Mark ^{[1
,2
]}

Krueger, James G. ^{[3
]}

Leung, Donald Y. M. ^{[1
,2
]}

机构：

[1] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA

[2] Univ Colorado, Dept Pediat, Aurora, CO USA

[3] Rockefeller Univ, Lab Invest Dermatol, New York, NY 10021 USA

[4] Weill Cornell Med Coll, Dept Dermatol, New York, NY USA

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2011年 / 131卷 / 06期

关键词：

NECROSIS-FACTOR-ALPHA; ATOPIC-DERMATITIS; PSORIATIC SKIN; CELL-DEATH; KAPPA-B; ACTIVATION; LOCALIZATION; EXPRESSION;

D O I：

10.1038/jid.2011.24

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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.

引用

页码：1272 / 1279

页数：8

共 24 条

[1] IL-4 and IL-13 negatively regulate TNF-α- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3 [J].