title: TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier.
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.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.
authors.forename: Byung Eui
authors.initials: BE
authors.lastname: Kim
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Gilleaudeau
authors.forename: Irma R
authors.initials: IR
authors.lastname: Cardinale
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D015536:Down-Regulation; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C064554:loricrin; D048031:JNK Mitogen-Activated Protein Kinases