Challenge to the developmental study of new biomarker and new treatment in recalcitrant allergic skin disease

1) AD患者皮损角质层IL-18水平显著高于健康对照组，并与SCORAD、血清IL-18、IgE、乳酸脱氢酶（LDH）、胸腺及活化调节趋化因子（TARC）、血嗜酸性粒细胞和经皮失水（TEWL）水平相关。在血清IgE<1500 IU mL的AD组中，金黄色葡萄球菌定殖的患者角质层IL-18水平明显高于未定殖的患者。从这些结果可以得出结论，表皮IL-18的产生与AD的严重程度有关，金黄色葡萄球菌的定植似乎有助于这种IL-18的产生，特别是在IgE产量相对较低的AD组中，胶带剥离提供了一种简单且无创的ELISA方法来评估表皮IL-18的产生。瘙痒是牛皮癣的常见症状，影响生活质量。银屑病病变中有更多的y - c纤维。两种细胞外分子，神经生长因子（NGF）和信号素- 3a，调节c -纤维的延伸。本研究采用免疫组织化学和定量反转录PCR方法，定量分析了这2个分子在银屑病和健康皮肤活检标本中的表达水平。与健康样本相比，银屑病样本中Semaphorin-3A的表达较低，而NGF的表达较高。银屑病皮肤表皮的c纤维神经支配也增加。Semaphorin-3A mRNA表达与银屑病瘙痒强度和严重程度呈负相关。我们认为信号素- 3a的减少和NGF表达水平的增加可能触发c纤维的生长，导致瘙痒。打喷嚏和鼻黏膜持续瘙痒是过敏性鼻炎（AR）的令人痛苦的症状。最近的研究表明，鼻鼻甲感觉神经元的过度神经支配是打喷嚏和瘙痒的潜在原因之一。由于Sema3A （Sema3A）先前已被证明可以限制感觉神经元的神经分布，因此推测Sema3A在鼻黏膜中的表达减少可能导致过敏。卵清蛋白致敏AR小鼠模型分析显示，Sema3A在鼻上皮中的表达降低，同时鼻甲固有层神经纤维密度增加。在救援实验中，经鼻给药重组Sema3A可减轻AR模型小鼠的打喷嚏和鼻摩擦症状。此外，组织学检查还显示，sema3a处理的鼻甲骨固有层神经纤维密度降低。这些结果提示，鼻部过敏性AR可能与Sema3A表达减少有关，鼻内给药Sema3A可能为AR治疗提供一种缓解过敏症状的新途径。3) CTP在体外促进人真皮成纤维细胞和小鼠皮肤透明质酸的生成。口服CTP可显著降低干性皮肤模型小鼠TEWL，抑制抓伤行为。ctp处理小鼠表皮内神经生长明显受到抑制。定量PCR分析和免疫组化研究显示，CTP可消除丙酮诱导的NGF升高和Sema3A水平降低。从这些结果可以得出结论，口服CTP可以改善皮肤干燥，并使表皮轴突引导因子正常化，同时减少瘙痒。CTP可能是一种治疗皮肤干燥和瘙痒的新方法。少

1) IL-18 levels in the horny layer were significantly higher in the skin lesions of patients with AD than in healthy controls and correlated with SCORAD, levels of serum IL-18, IgE, lactate dehydrogenase(LDH), thymus and activation-regulated chemokine(TARC), blood eosinophils and transepidermal water loss(TEWL). In the AD group with serum IgE<1500 IU mL, significantly higher IL-18 levels were observed in the horny layer of patients colonized with S. aureus compared with those who were not. From these results, it may be concluded that epidermal IL-18 production is associated with the severity of AD, that staphylococcus aureus colonization seems to contribute to this IL-18 production, especially in the AD group with relatively low IgE production, and that tape stripping provides an easy and noninvasive method to assess epidermal IL-18 production by ELISA. 2-1) Pruritus is a common symptom of psoriasis, which affects quality of life. This symptom accompanies the hyperinnervation of sensor … More y C-fibres in psoriatic lesions. Two extracellular molecules, nerve growth factor(NGF) and semaphorin-3A, regulate C-fibre extension. In this study, the expression levels of these 2 molecules in biopsy specimens from psoriatic and healthy skin were quantified by immune-histochemistry and quantitative reverse-transcription PCR. Semaphorin-3A expression was lower in the psoriatic samples compared with the healthy samples, whereas NGF was higher. C-fibre innervation in the epidermis was also increased in psoriatic skin. Semaphorin-3A mRNA expression was negatively correlated with itch intensity and severity of psoriasis. We propose that decreased semaphorin-3A and increased NGF expression levels may trigger the outgrowth of C-fibres, leading to pruritus. 2-2) Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis(AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A(Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment. 3) CTP enhanced hyaluronic acid production in human dermal fibroblasts in vitro and in murine skin in vivo. Oral administration of CTP in acetone-induced dry skin model mice significantly decreased TEWL and suppressed scratching behavior. Intraepidermal nerve growth was dramatically inhibited in CTP-treated mice. Quantitative PCR analysis and immunohistochemical study revealed that CTP abolished the increased NGF and decreased Sema3A levels induced by acetone treatment. From these results, it may be concluded that oral administration of CTP improves dry skin and normalizes axon-guidance factors in the epidermis in addition to reducing pruritus. CTP may be used in a new therapeutic strategy against dry skin and pruritus. Less