肿瘤坏死因子-α 通过 c-Jun N 端激酶下调丝聚蛋白和兜甲蛋白：TNF-α 拮抗剂改善皮肤屏障的作用。
TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier.
机构信息
Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.
出版信息
J Invest Dermatol. 2011 Jun;131(6):1272-9. doi: 10.1038/jid.2011.24. Epub 2011 Feb 24.
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.
摘要
丝聚蛋白（FLG）、兜甲蛋白（LOR）和 Involucrin 是重要的表皮屏障蛋白。由于银屑病的特征是肿瘤坏死因子-α（TNF-α）过度表达和皮肤屏障受损，我们研究了银屑病患者表皮屏障蛋白的表达情况，以及 TNF-α 是否调节其表达。我们发现，银屑病患者的皮损和非皮损皮肤中丝聚蛋白和兜甲蛋白的表达减少。我们还发现，在银屑病中，TNF-α 与表皮屏障蛋白的表达存在相关性。研究发现，TNF-α 通过 c-Jun N-末端激酶依赖性途径调节丝聚蛋白和兜甲蛋白的表达。重要的是，我们报告称，用 TNF-α 拮抗剂治疗银屑病患者可显著增强表皮屏障蛋白的表达。我们的研究表明，TNF 抑制屏障蛋白的表达，而 TNF-α 拮抗剂可能通过改善屏障蛋白的表达来促进银屑病患者的临床改善。
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