降钙素基因相关肽对HaCaT细胞表达血管内皮生长因子的调控

目的 探讨降钙素基因相关肽(CGRP)对角质形成细胞表达和分泌血管内皮生长因子(VEGF)的调控.方法 用实时定量PCR(RT-PCR)方法检测CGRP、CGRP1型受体拮抗剂CGRP8-37、细胞外信号调节激酶ERK1/2特异性的抑制剂PD98059、p38MAPK特异性拮抗剂SB203580对HaCaT角质形成细胞表达VEGFmRNA水平的影响;用酶联免疫吸附方法检测HaCaT细胞分泌至培养液中VEGF蛋白的水平.结果 CGRP时间依赖性地促进HaCaT细胞表达VEGFmRNA和分泌VEGF蛋白;CGRP8-37和PD98059均可明显抑制CGRP刺激的HaCaT细胞表达和分泌VEGF,SB203580不能减弱CGRP刺激的VEGF表达和分泌.结论 CGRP可以上调HaCaT细胞表达和分泌VEGF,CGRP1型受体及其相关的ERK1/2信号通路参与其调控.     

人乳头瘤病毒感染对朗格汉斯细胞影响机制的研究进展

人乳头瘤病毒感染时,皮肤朗格汉斯细胞的数量、形态、分布及功能发生一系列改变,尤其功能受损被认为与导致人乳头瘤病毒逃逸宿主免疫、造成持续感染有关.研究提示,人乳头瘤病毒感染时某些细胞因子或蛋白酶等,如前列腺素E2及其主要限速酶、巨噬细胞炎性蛋白3α、转化生长因子-β、上皮细胞钙黏素、胰岛蛋白、肿瘤坏死凶子相关的凋亡诱导配体等的异常表达可能影响朗格汉斯细胞功能活化.但确切机制有待进一步研究证实.

Abstract：

The infection of human hosts with human papillomavirus (HPV) can lead to a series of changes in the number, morphology, distribution and function of cutaneous Langerhans cells. In particular, the functional impairment of Langerhans cells is considered to be associated with the escape of HPV from host immunity and persitent HPV infection. Studies have suggested that the abnormal expression of some cytokines or proteases, such as prostaglandin E2 and its major rate-limiting enzyme, macrophage inflammatory protein 3 alpha, transforming growth factor-beta, E-cadherin, langerin/CD207, tumor necrosis factor-related apoptosisinducing ligand, may affect the activation and function of Langerhans cells. Further studies are required to explore the exact mechanisms.     

降钙素基因相关肽在银屑病发病机制中的研究进展

银屑病发病机理目前尚不完全清楚,研究人员在对皮损的组织病理研究中发现,银屑病的组织病理表现及皮肤内神经纤维的过度增生均与皮损内高水平的神经介质相关,基于相关研究确立了银屑病神经源性炎症发病机制的概念［１］……     

降钙素基因相关肽对HaCaT细胞增殖和分泌神经生长因子的影响

目的研究降钙素基因相关肽(CGRP)对HaCaT细胞增殖和神经生长因子(NGF)分泌的影响。方法以不同浓度(10-10～10-7mol/L)的CGRP作用于HaCaT细胞,MTT法检测HaCaT细胞增殖情况,ELISA法检测细胞上清液中NGF浓度的变化。结果CGRP促HaCaT细胞增殖作用的强度与CGRP的浓度和作用时间有关:CGRP浓度为10-10～10-8mol/L时,其促增殖作用呈浓度依赖性;当浓度上升至10-7mol/L时促增殖作用反而减弱;CGRP作用48h促增殖作用最强。HaCaT细胞上清液中NGF浓度随CGRP浓度升高和作用后时间延长而增加。结论CGRP可促进HaCaT细胞增殖和分泌NGF。NGF分泌增加可能是CGRP促进HaCaT细胞增殖的原因之一。     

朗格汉斯细胞功能的新认识

朗格汉斯细胞是位于皮肤表皮的组织特异性不成熟树突细胞,其感知、传递外界环境的信号刺激并指导后续的免疫应答.早期研究显示,朗格汉斯细胞具有强大的诱导免疫应答的能力,在启动T细胞特异性免疫应答中起着重要的作用.而最近的一系列研究提示,朗格汉斯细胞的主要作用可能是诱导免疫耐受,其机制可能与特异性T细胞的清除、调节性T细胞的产生、协同刺激因素等相关.因此,朗格汉斯细胞不仅是免疫反应的哨兵,更是人体皮肤环境平衡的维护者.     

降钙素基因相关肽对HaCaT细胞一氧化氮合酶表达的影响

目的 研究降钙素基因相关肽对体外培养角质形成细胞HaCaT株神经型一氧化氮合酶(NOS)mRNA、蛋白表达和NO释放的调节作用。方法 应用NO试剂盒(酶法)检测培养细胞上清液中NO水平,RT-PCR和免疫组化(SP)方法检测HaCaT细胞神经型NOSmRNA和蛋白的表达水平。结果 体外正常培养的HaCaT细胞表达和释放基础水平的神经型NOS和NO,降钙素基因相关肽上调HaCaT细胞神经型NOS表达和NO释放,降钙素基因相关肽受体抑制剂CGRP-8-37抑制降钙素基因相关肽的作用。结论 降钙素基因相关肽诱导角质形成细胞表达神经型NOS并促进神经型NO释放。     

S100+朗格汉斯细胞与尖锐湿疣复发的相关性研究

尖锐湿疣发病和复发与局部免疫抑制有关已得到公认,但免疫抑制的确切机制不甚明确。有研究提不S100⁺朗格汉斯细胞(LC)可能为活化的LC亚群,对环境改变较为敏感。     

内皮素和降钙素基因相关肽与变应性皮肤血管炎相关性研究

变应性皮肤血管炎（allergic cutaneous vasculitis，ACV）是一种主要累及真皮浅层小血管和毛细血管的过敏性、炎症性皮肤病。内皮素（endothelins，Err）和降钙素基因相关肽（calcitonin gene related peptide，CGRP）是两种相互拮抗的具有多种生物学效应的神经肽，在机体内分布广泛，对各系统特别是心血管系统具有重要调节作用。笔者采用放射免疫法测定37例ACV患者血浆中ET和CGRP水平，旨在探讨ET和CGRP在ACV发病中的作用及其临床意义。     

白癜风患者血浆与皮肤疱液降钙素基因相关肽测定

降钙素基因相关肽（CGRP）是重要的神经递质及免疫调节因子。研究旨在观察其是否可能与白癜风的发病有关。采用放射免疫分析法测定40例白癜风血浆CGRP浓度，并与正常对照作比较；同时测定部分患者白斑与非白斑处皮肤疱液CGRP浓度。结果显示寻常型与进展期白癜风血浆CGRP水平增高，白斑与非白斑处皮肤疱液其浓度无差别，认为CGRP与白癜风的发病可能存在一定关系。     

降钙素基因相关肽在银屑病斑块型皮损的分泌与表达

为了解精神心理刺激诱发加重银屑病的原因,探讨神经肽在银屑病发病机理中的作用,研究了降钙素基因相关肽（ＣＧＲＰ）在银悄病皮损中的分泌与表达,并确定ＣＧＲＰ作用的靶细胞,应用特异性放射免疫反相法分析,测定３２例建党型银屑病慢性斑块型皮损组织提取液中ＣＧＲＰ的含量,用抗生物素蛋白－生物素－过氧化物酶复合法和兔抗人ＣＧＲＰ抗体进行免疫组化染色,观察ＣＧＲＰ分泌表达的部位和作用的靶细胞。结果建党型银屑病慢性     

Occurrence of substance P,vasoactive intestinal peptide,and calcitonin gene-related peptide in dermographism and cold urticaria

Summary Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.     

Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance ( P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis. Received: 3 March 1997     

Cutaneous vascular response to calcitonin gene-related peptide in psoriasis and normal subjects

To determine whether cutaneous blood vessels in subjects with psoriasis possess a generalized inherently abnormal response to neuropeptides, the effect of three doses of intradermally injected calcitonin gene-related peptide (CGRP) on skin blood flow in normal subjects (n= 10), and on clinically normal skin (greater than 5 cm from psoriatic lesions) in subjects with psoriasis (n= 9) was measured using a laser Doppler technique. Calcitonin gene-related peptide caused a dose-dependent increase in local blood flow in both psoriatic and normal subjects, which was not statistically different between the two groups. This study has shown that the cutaneous vasculature at sites distant from lesions of psoriasis (> 5 cm) is not inherently different from normal skin in its response to CGRP.     

Neuropeptides and Langerhans cells

Abstract: The immune system and nervous system are intimately related. In addition to neuroendocrine mechanisms, neuropeptides have a variety of effects on immune cells and are responsible at least in part for neurogenic inflammation. The presence of neuropeptides in the skin has been well documented. The influence of neuropeptides on Langerhans cells is the focus of this paper. The physical presence and effects of calcitonin gene-related peptide on Langerhans cells is emphasized. Discussion also includes the putative inflammatory and immunologic roles of vasoactive intestinal peptide, substance P, neurotensin, neuropeptide Y, and somatostatin in the skin.     

Effects of UVB on fascin expression in dendritic cells and Langerhans cells

BACKGROUND: Fascin is an actin-binding protein that regulates the rearrangement of cytoskeletal elements and their interactions with the cell membrane. Previous studies have indicated that fascin expression is enhanced in DC upon maturation and plays a critical role in T cell activation. Ultraviolet irradiation exerts immunosuppressive effects. OBJECTIVE: We examined the effects of UVB irradiation on the interaction of DC/LC with T cells through fascin. METHOD: Murine bone marrow-derived DC (BM-DC) were induced by recombinant murine GM-CSF and LPS, and UVB irradiation was applied prior to supplementation with LPS. I-A(+) cells (Langerhans cells (LC)) in the epidermal cell suspensions were exposed to UVB irradiation at the beginning of the 24-h culture. BM-DC and LC were analysed by immunohistochemical staining and flow cytometric analyses. To evaluate the effects of UVB irradiation on DC-T cell binding, we examined the clustering of BM-DC with allogeneic CD4(+) T cells under a confocal microscope. RESULTS: Fascin expression in BM-DC and LC was decreased by UVB irradiation. Furthermore, UVB irradiation reduced the ability of BM-DC to cluster with allogeneic CD4(+) T cells. Polarization of fascin and filamentous actin (F-actin) at the point of contact of BM-DC with T cells was also disturbed by UVB irradiation. CONCLUSION: These results suggest that the suppression of fascin expression by UVB irradiation down-regulates the rearrangement of the cytoskeleton and, thereby, antigen presentation in DC/LC.     

温热对HPV感染皮肤中朗格汉斯细胞的影响

目的 探讨不同温热条件处理后的正常皮肤/尖锐湿疣皮损组织中朗格汉斯细胞（LC）的形态、数量及迁移。方法 利用37 ℃、42 ℃、45 ℃不同的温热条件处理置于培养液中的离体尖锐湿疣皮损（16例）和正常皮肤组织（15例），采用免疫组化和流式细胞分析方法测定LC形态、数量和迁移的变化。结果 表皮中LC数量随着温度的增高而减少，正常皮肤组织表皮内LC数量分别为：782.40 ± 114.88（37 ℃），649.44 ± 119.40（42 ℃），510.88 ± 118.64（45 ℃）；疣体组织表皮内LC数量分别为：646.04 ± 135.67 （37 ℃）、489.38 ± 118.19 （42 ℃）、387.93 ± 110.15 （45 ℃ ）；LC树突变短、减少或消失。温热促进LC迁移至培养液中。不同温度下，游走的LC表达CD1a的数量不同，正常皮肤组织游走至培养液中LC表达CD1a的比率分别是0.19% ± 0.18%（37 ℃），0.89% ± 0.19%（42 ℃），1.59% ± 0.28%（45 ℃）；尖锐湿疣组织分别为0.62% ± 0.31%（37 ℃），2.31% ± 0.54%（42 ℃），6.33% ± 0.98%（45 ℃）。结论 温热能够促进LC的迁移，籍此有可能增强LC在免疫应答中的抗原提呈作用。     

Langerhans cells of human mucosa

The ontogeny of human LC and their presence in all Malpighian epithelia underline their important role in immunoregulation of the skin and mucous membranes. LC are also found in buccal and esophageal mucosa, in cornea and conjunctiva, in pulmonary, vesical, vaginal and cervical epithelia as well as in placenta villi. In all these Malpighian epithelia, the presence of DR + LC is necessary and essential for the surveillance function against allergo-antigens and the emergence of neo-antigens associated with malignant transformations.     

Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis

Background  Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.
Objectives  To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-γ production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.
Methods  Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-γ production and HLA-DR expression were measured in both CLA+ and CLA− T-cell subsets by flow cytometry.
Results  CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD ( P  <   0·05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls ( P  <   0·05). Memory T cells incubated with CGRP also showed an increase in IL-13 ( P  <   0·05) and HLA-DR ( P  <   0·05) in CLA+ T cells from patients with AD compared with controls, but not in CLA− T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-γ ratio was increased in patients with AD after cells were cultured with CGRP ( P  <   0·05).
Conclusions  Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD.     

Effects of pimecrolimus versus triamcinolone on Langerhans cells after UV exposure

Abstract: Background/Purpose: Pimecrolimus is a topical immunomodulator for atopic dermatitis. Concerns regarding malignancy risk resulted in its black box warning in 2006. The purpose of this study is to determine the effects of pimecrolimus on Langerhans cells (LC), mediators of the cutaneous immunity UV‐irradiated skin. Methods: A RCT was conducted investigating pimecrolimus 1% cream vs triamcinolone 0.1% cream on UV‐irradiated epidermal LC on 20 healthy volunteers. Punch biopsies were stained with antibodies to CD1a, HLADR and CD83. Results: Triamcinolone caused more depletion in UV‐irradiated CD1a⁺ epidermis relative to pimecrolimus treatment. (P = 0.030). Using HLA‐DR as a pan‐marker for APCs, pimecrolimus caused marginally less depletion than triamcinolone (P = 0.013). Using anti‐CD83 as a maturation marker, UV‐irradiated skin treated with pimecrolimus showed more mature LC than skin treated with triamcinolone (P = 0.00090). Conclusion: UV‐induced changes in LC are minimally affected by pimecrolimus, compared with triamcinolone.