特应性皮炎相关细胞因子对皮肤屏障的影响

【摘要】 皮肤是人体最大的器官,是一个重要的屏障。特应性皮炎患者存在皮肤屏障功能异常,同时其细胞因子的组成与健康人不同。在特应性皮炎患者皮肤中发现的许多细胞因子能够影响角质形成细胞的分化和角化过程。本文综述了特应性皮炎相关细胞因子的最新进展及其对皮肤屏障功能的影响,这些结果有利于了解特应性皮炎的发病机制,并可能为特应性皮炎的治疗提供新的方向。     

特应性皮炎与皮肤微生态的研究进展

特应性皮炎是一种慢性、复发性、炎症性皮肤病.其发病机制复杂,在遗传基础上,表皮屏障功能异常、环境过敏原暴露、金黄色葡萄球菌定植等诱发的免疫炎症反应均参与其发病.皮肤微生态是皮肤表面微生物构成的复杂生态系统,近年研究提示,微生态异常在特应性皮炎的发病过程中起重要作用,特应性皮炎患者的皮肤除了存在金黄色葡萄球菌定植增多外,还存在表皮葡萄球菌等其他微生物数量和功能的改变.因此,进一步揭示各种微生物群落与特应性皮炎发病的关系,有助于特应性皮炎的防治.     

皮肤屏障与特应性皮炎

皮肤屏障结构与功能异常是特应性皮炎的主要病理生理改变,而皮肤屏障的修复已成为特应性皮炎的基础治疗。该文就皮肤屏障主要结构及与特应性皮炎发病的关系以及皮肤屏障修复在特应性皮炎治疗中的作用作一简要阐述。     

特应性皮炎的体外3D皮肤模型

特应性皮炎是一种慢性炎症性皮肤病,其病理机制涉及表皮屏障功能破坏、皮肤微生物组异常和2型炎症免疫失调之间复杂的相互作用.随着组织工程技术发展,3D皮肤模型已与正常人体皮肤结构接近.通过模拟特应性皮炎的病理机制,许多研究者成功构建出特应性皮炎的3D皮肤模型.该模型被应用于特应性皮炎的病理机制研究、药物筛选方面,是进行特应...     

特应性皮炎的合并症及相关的综合征

特应性皮炎是一种不仅局限于皮肤的炎症性疾病。除皮肤损害外,患者常合并哮喘、过敏性鼻炎和食物过敏,其皮肤对细菌和病毒的易感性增加,一些免疫缺陷综合征常伴有特应性皮炎表现。近年还发现,特应性皮炎与注意缺陷多动障碍等行为异常密切相关,其机制尚不完全清楚。进一步阐明特应性皮炎与躯体或精神障碍合并症之间的潜在生物学机制,可能会增加临床医师对特应性皮炎发病机制的理解,并有助于研发靶向干预特应性皮炎的治疗或预防措施。     

特应性皮炎与皮肤微生物态的关系

特应性皮炎是一种慢性、周期性、瘙痒性皮肤病。近年来,我国患病人数迅速上升,尽管越来越多的人深受其困扰,但目前病因尚不清楚,近年来发现皮肤微生物态对全身免疫功能及局部皮肤免疫功能有影响,皮肤屏障完整性的改变会导致皮肤微生物多样性的改变和皮肤菌群的紊乱,诱发并加重特应性皮炎。特应性皮炎的患者与健康人相比,发生皮肤感染的风险也更高。因此,特应性皮炎与皮肤微生物态的关系也成为近年来研究的热点。     

不同原因导致敏感性皮肤的皮肤生理功能测试及临床意义

目的:探讨痤疮、激素依赖性皮炎、特应性皮炎和干燥性湿疹等不同原因导致敏感性皮肤的皮肤生理功能特点,指导敏感性皮肤的护理和治疗.方法:选取各种原因导致的敏感性皮肤受试者154名,均为女性.运用无创性皮肤生理功能测试仪测量受试者的皮肤皮脂含量、角质层含水量和经表皮水分丢失(TEWL).结果:与单纯敏感性皮肤比较,痤疮组皮脂含量较高(P＜0.05),激素依赖性皮炎组TEWL值较高(P＜0.05),特应性皮炎和干燥性湿疹组皮脂含量、角质层含水量较低,而TEWL值较高(P＜0.05),其余参数比较差异无统计学意义;与痤疮导致的敏感性皮肤比较,激素依赖性皮炎组皮脂含量较低(P＜0.05),TEWL值较高(P＜0.05),特应性皮炎和干燥性湿疹组皮脂含量、角质层含水量较低(P＜0.05),而TEWL值较高(P＜0.05),其余参数比较差异无统计学意义;与激素依赖性皮炎导致的敏感性皮肤比较.特应性皮炎和干燥性湿疹组皮脂含量较低(P＜0.05),其余参数比较差异无统计学意义.结论:不同原因导致敏感性皮肤的皮肤屏障功能状态不完全一致,应根据不同病因对敏感性皮肤进行治疗和护理.     

特应性皮炎皮肤屏障缺陷的研究进展

特应性皮炎是一种常见的慢性炎症性皮肤疾病,病因复杂,涉及患者与环境因素间的相互作用。皮肤屏障是一种机械性和免疫性的屏障,在阻止微生物及过敏原渗透以及免疫监视、保持动态平衡中起关键作用。特应性皮炎的发病机制涉及皮肤屏障功能与结构的破坏及功能的缺陷。该文对维持特应性皮炎皮肤屏障功能所必需的成分改变进行了综述。     

肠-脑-皮肤轴与特应性皮炎

特应性皮炎作为世界范围内常见的皮肤病,病因不明,临床上具有慢性、复发性等特点,严重影响患者的生活质量。目前发现慢性皮肤病和心理疾病共病率逐年上升,且跨学科研究表明肠道、肠道微生物异常以及心理疾病与皮肤疾病之间存在着关联性的通信轴,例如既往已经证实的肠-脑轴、脑-皮肤轴。因此肠道功能的完整性和肠道菌群的平衡状态可能在皮肤炎症和情绪行为中起到中介作用,即存在肠-脑-皮肤轴。本文探讨了肠道菌群和心理因素对特应性皮炎发病及病情发展的影响,以及肠-脑-皮肤轴对特应性皮炎的作用机制,并以中医理论进行阐述,拟利用16SrRNA测序法从"健脾"的方面观察中医药通过作用该通信轴治疗特应性皮炎远期疗效。     

特应性皮炎微生态研究进展

特应性皮炎(atopic dermatitis,AD)是一种慢性、复发性、炎症性、瘙痒性皮肤病。其发病机制复杂,与遗传、环境、免疫炎症反应、皮肤屏障破坏、皮肤表面微生态异常等有关。近几年AD患者皮肤微生物群的作用已经被广泛研究。本文就特应性皮炎微生态做一简要综述。     

The changing face of dermatology out-patient referrals in the south-east of Scotland

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.     

Changes of epidermal mu-opiate receptor expression and nerve endings in chronic atopic dermatitis

There is increasing evidence that neuropeptides such as a substance P, neurotrophins or beta-endorphin, an endogenous agonist for mu-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. mu-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of mu-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of mu-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the mu-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the 'intensity' and 'pattern' hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that 'itch' is elicited in the epidermal unmyelinated nerve C-fibers and 'pain' in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the 'layer hypothesis'.     

Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates

Atopic dermatitis is a chronic inflammatory skin disease characterized by impaired epidermal barrier function, inflammatory infiltration, extensive pruritus and a clinical course defined by symptomatic flares and remissions. The mechanisms of disease exacerbation are still poorly understood. Clinical occurrence of atopic dermatitis is often associated with psychological stress. In response to stress, upregulation of neuropeptide mediators in the brain, endocrine organs, and peripheral nervous system directly affect immune and resident cells in the skin. Lesional and non-lesional skin of patients with atopic dermatitis demonstrates increased mast cells and mast cell-nerve fiber contacts. In the setting of stress, sensory nerves release neuromediators that regulate inflammatory and immune responses, as well as barrier function. Progress towards elucidating these neuroimmune connections will refine our understanding of how emotional stress influences atopic dermatitis. Moreover, psychopharmacologic agents that modulate neuronal receptors or the amplification circuits of inflammation are attractive options for the treatment of not only atopic dermatitis, but also other stress-mediated inflammatory skin diseases.     

Skin barrier function in patients with completely healed atopic dermatitis

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.     

神经营养素与特应性皮炎发病机制的进展

神经营养素是一个复杂的分子家族,已经发现它们对中枢神经系统以外的组织亦有重要作用。越来越多的研究显示,它们在炎症性皮肤病,如特应性皮炎的发病中可能起了重要的作用,在特应性皮炎中,虽然已经发现人类皮肤的各种细胞能分泌一系列的神经营养因子,但它们与皮损处的神经分布的关系还未能明确阐述。综述神经营养素家族在特应性皮炎发病机制中的研究进展。     

Effects of high-affinity nerve growth factor receptor inhibitors on symptoms in the NC/Nga mouse atopic dermatitis model

BACKGROUND: Nerve growth factor (NGF) is an important substance in the skin, where it modulates nerve maintenance and repair. However, the direct link between NGF and pruritic diseases such as atopic dermatitis is not yet fully understood. Our previous study showed that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice. NGF mediates its effects by binding to two classes of transmembrane receptors, a high-affinity receptor (tropomyosin-related kinase A, TrkA) and a low-affinity receptor (p75). OBJECTIVES: To determine the significance of NGF receptors in the pathogenesis of atopic dermatitis, the effects of TrkA inhibitors AG879 and K252a on the symptoms of NC/Nga mice were evaluated. METHODS: Male NC/Nga mice with severe skin lesions were used. AG879 or K252a was applied to the rostral part of the back of mice five times a week. The dermatitis score for the rostral back was assessed once a week. The scratching behaviour was measured using an apparatus, MicroAct (Neuroscience, Tokyo, Japan). Immunofluorescence examinations were made in the rostral back skin for nerve fibres, NGF and TrkA receptor. RESULTS: Repeated applications of AG879 or K252a significantly improved the established dermatitis and scratching behaviour, and decreased nerve fibres in the epidermis. NGF was observed more weakly in keratinocytes, and a lower expression of TrkA was observed in stratum germinativum of the epidermis of mice treated with AG879 or K252a compared with those treated with vehicle. CONCLUSIONS: We suggest that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions via the high-affinity NGF receptor. These findings provide a new potential therapeutic approach for the amelioration of symptoms of atopic dermatitis.     

精神应激在特应性皮炎中的作用

特应性皮炎是一种慢性、复发性、炎症性皮肤疾病,发病机制不明。特应性皮炎病情的复发与精神应激事件密切相关。本文综述了精神应激在特应性皮炎发病中的作用,一方面通过复杂的神经内分泌免疫网络影响炎症细胞的功能,另一方面,精神应激破坏皮肤屏障功能,诱发级联免疫反应,加重病情。     

No increased skin reactivity in subjects with allergic rhinitis during the active phase of the disease

Data on skin reactivity in patients with respiratory atopy without atopic dermatitis are scarce and controversial. Our purpose was to assess whether skin reactivity in patients with seasonal allergic rhinitis varies according to the phase of the disease and the possible release of inflammatory mediators acting on the skin during the pollen season. The volar forearm skin of eleven patients with seasonal allergic rhinitis without atopic dermatitis was challenged with a single exposure to sodium lauryl sulfate. The skin response was evaluated instrumentally over 72 h by transepidermal water loss, capacitance and echogenicity measurements for the assessment of skin damage and the inflammatory response. Tests were performed in winter and repeated in spring in seasonal allergic rhinitis patients, when they showed respiratory symptoms. Fifteen subjects with atopic dermatitis underwent the same experimental procedure in winter as a control population. Baseline and postexposure values were similar both in winter and in spring in seasonal allergic rhinitis patients. After sodium lauryl sulfate challenge, atopic dermatitis patients showed a higher degree of skin barrier damage and inflammation compared to patients with seasonal allergic rhinitis. These findings suggest that subjects with seasonal allergic rhinitis without atopic dermatitis have normal epidermal barrier function and normal skin reactivity during both the inactive and the active phase of the disease. Inflammatory mediators possibly released by mucous membranes during active allergic rhinitis do not influence skin barrier function.     

Neuropeptides in the skin of patients with atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuro-peptides were examined in lesional and non-lesional skin of AD patients (n= 5) and in normal controls (n= 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9·5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0·05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients hut no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetyleholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD.     

Itch in atopic dermatitis - pathophysiology and treatment

Pruritus is an essential feature of atopic dermatitis with a high impact on the quality of life. Although the pathophysiology of atopic dermatitis itch is not fully understood, recent studies have demonstrated that a variety of mechanisms contribute to the induction and maintenance of the symptom. For example, an increased number of cutaneous nerve fibers and neuropeptides were identified in atopic dermatitis skin. Histamine and histamine 4 receptor as well as interleukin 31 are novel key players identified in itch induction, in addition to inflammatory cells such as mast cells, eosinophils and lymphocytes. The new findings suggest that target-specific therapies are most likely to control atopic dermatitis itch. To date, only few therapies are available and controlled studies are pending.