Interleukin-4 suppresses the enhancement of ceramide synthesis and cutaneous permeability barrier functions induced by tumor necrosis factor-α and interferon-γ in human epidermis
Interleukin-4 suppresses the enhancement of ceramide synthesis and cutaneous permeability barrier functions induced by tumor necrosis factor-α and interferon-γ in human epidermis
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DOI：
10.1111/j.0022-202x.2005.23651.x
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发表时间：
2005-04-01
影响因子：
6.5
通讯作者：
Katagiri, K
中科院分区：
文献类型：
--
作者：
Hatano, Y;Terashi, H;Katagiri, K
神经酰胺是构成皮肤通透性屏障的角质层(SC)细胞外脂双层的组成部分。神经鞘磷脂酶(SMase)和葡萄糖脑苷酶(GCase)催化SC神经酰胺的产生。酸性神经酰胺酶(ACID-CDase)催化SC中神经酰胺的水解。我们检测了辅助性T细胞(Th)1和Th2细胞因子对酸性CDase、酸性CDase和GCase基因转录水平、神经酰胺水平以及人表皮透皮失水(TEWL)程度的影响，以确定这些细胞因子是否影响通透性屏障功能。肿瘤坏死因子(TNF)-α和干扰素(干扰素)-γ可促进人表皮酸性单酶和GCase转录本水平及神经酰胺含量，而白介素4可抑制这些作用。然而，在浸泡条件下培养的表皮角质形成细胞中，没有观察到IL-4类似的抑制作用。与此结果一致的是，肿瘤坏死因子-α和干扰素-γ抑制了TEWL，IL-4也抑制了这些作用。Th1/Th2之间的平衡可能通过调节神经酰胺的产生而影响表皮通透性屏障的构建和/或修复。
Ceramide is an integral part of the extracellular lipid bilayer of the stratum corneum (SC) that forms the permeability barrier of the skin. The production of SC ceramides is catalyzed by sphingomyelinase (SMase) and glucocerebrosidase (GCase). Acid-ceramidase (acid-CDase) catalyzes the hydrolysis of ceramide in the SC. We examined the effects of T helper (Th)1 and Th2 cytokines on levels of transcripts of genes for acid-CDase, acid-SMase, and GCase, on levels of ceramide, and on the extent of transepidermal water loss (TEWL) in the human epidermis in an effort to determine whether these cytokines affect the permeability barrier functions. Levels of transcripts for acid-SMase and GCase and the amount of ceramide in human epidermal sheets were enhanced by tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and these effects were inhibited in the presence of interleukin (IL)-4. In epidermal keratinocytes cultured under submerged conditions, however, no similar inhibitory effects of IL-4 were observed. Consistent with these results, TEWL was suppressed by TNF-alpha and IFN-gamma, and these effects were also inhibited by IL-4. The balance between Th1 and Th2 might affect the construction and/or the repair of the epidermal permeability barrier via regulation of the production of ceramide.