期刊
BRITISH JOURNAL OF DERMATOLOGY
卷 165, 期 3, 页码 492-498出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2133.2011.10400.x
关键词
-
类别
资金
- MRC
- NIHR Biomedical Research Centre Programme and Comprehensive Local Research Network
- MRC [MC_U137881017, G0701693] Funding Source: UKRI
- Medical Research Council [G1000800h, G0701693, MC_U137881017] Funding Source: researchfish
Background The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Interleukin (IL)-22 is upregulated in lesional AE tissue, but its effects on filaggrin expression and genes associated with epidermal function have not yet been comprehensively addressed. Objectives To investigate the effects of IL-22 on expression of filaggrin and genes encoding proteins relevant to epidermal function. Methods Microarray analysis was performed on IL-22-stimulated HaCaT keratinocytes. Filaggrin protein level was assessed by an intracellular enzyme-linked immunosorbent assay (ELISA) and Western blot in HaCaT cells and the findings were validated in primary keratinocytes. Results Exposure to IL-22 cytokine resulted in a downregulation of profilaggrin mRNA expression in HaCaT keratinocytes. The expression of genes involved in enzymatic processing of profilaggrin as well as the generation of natural moisturizing factor was also altered. Furthermore, there was an upregulation of many transcripts encoding proteins of the S100 family. Profilaggrin/filaggrin downregulation was detected by intracellular ELISA and Western blot in HaCaT cells. The relevance to the primary setting was confirmed in primary keratinocytes by Western blot. Conclusions IL-22 downregulates profilaggrin/filaggrin expression in keratinocytes at both mRNA and protein levels and affects genes relevant to epidermal function. This novel pathway may have relevance to the pathogenesis and treatment of atopic and other skin disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据