MRC Human Immunology Unit, NIHR Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, U.K.
Br J Dermatol. 2014 Oct;171(4):771-8. doi: 10.1111/bjd.13199. Epub 2014 Sep 30.
Histamine is an abundant mediator accumulating in the skin of atopic patients, where it is thought to be derived from immune cells. While keratinocytes express histidine decarboxylase (HDC), levels of the enzyme in normal or diseased epidermis and factors that influence its expression in human keratinocytes are not known.
To assess levels of HDC in inflammatory skin diseases and factors influencing its expression.
Normal and filaggrin-insufficient human keratinocytes, organotypic epidermal models and skin samples were investigated for the expression of HDC. The effect of cytokines, bacterial and allergen stimuli exposure and functional changes in differentiation were evaluated in vitro.
We detected abundant expression of the HDC protein in all models studied; expression was increased in atopic skin samples. Filaggrin-insufficient keratinocytes maintained HDC levels, but exposure of keratinocytes to thymic stromal lymphopoietin, tumour necrosis factor-α, lipopolysaccharide (LPS) and house dust mite (HDM) extract increased HDC expression in vitro. Furthermore, filaggrin expression in cultured keratinocytes increased following histamine depletion.
Keratinocytes express abundant HDC protein, and the levels increase in atopic skin. LPS, HDM and cytokines, which are implicated in allergic inflammation, promote the expression of the enzyme and upregulate histamine levels in keratinocytes. Actively produced histamine influences keratinocyte differentiation, suggesting functional relevance of the axis to atopic dermatitis. The findings therefore identify a new point of therapeutic intervention.
组织胺是一种在特应性患者皮肤中蓄积的丰富介质，被认为来源于免疫细胞。虽然角质形成细胞表达组氨酸脱羧酶（HDC），但其在正常或患病表皮中的水平以及影响其在人角质形成细胞中表达的因素尚不清楚。
评估 HDC 在炎症性皮肤病中的水平及其表达的影响因素。
研究了正常和缺乏板层素的人角质形成细胞、器官型表皮模型和皮肤样本中 HDC 的表达情况。在体外评估了细胞因子、细菌和过敏原刺激暴露以及分化功能变化对 HDC 表达的影响。
我们在所有研究的模型中均检测到 HDC 蛋白的大量表达；在特应性皮肤样本中表达增加。缺乏板层素的角质形成细胞维持 HDC 水平，但角质形成细胞暴露于胸腺基质淋巴细胞生成素、肿瘤坏死因子-α、脂多糖（LPS）和屋尘螨（HDM）提取物可增加体外 HDC 的表达。此外，在培养的角质形成细胞中组胺耗竭后，板层素的表达增加。
角质形成细胞表达丰富的 HDC 蛋白，在特应性皮肤中其水平增加。LPS、HDM 和细胞因子，这些都与过敏炎症有关，可促进酶的表达并上调角质形成细胞中的组胺水平。主动产生的组胺影响角质形成细胞分化，提示该轴与特应性皮炎具有功能相关性。因此，这些发现确定了一个新的治疗干预点。
