趋化因子CCL22/CCR4在SLE发病中的作用

目的 探讨趋化因子CCL22及其受体CCR4在SLE发病中的作用和临床意义。方法 SLE患者48例和体检正常人26例为检测对象。采用酶联免疫吸附试验测定血浆中CCL22的浓度,流式细胞仪分析法测定外周血趋化因子受体CCR4的水平。结果 SLE患者血浆中CCL22的水平（227.03 ± 122.84 ng/L）较正常人对照组（369.53 ± 79.10 ng/L）降低（P < 0.05）;SLE患者有肾损组CCL22水平（168.0 ± 61.83 ng/L）较无肾损组（292.77 ± 163.45 ng/L）明显降低（P < 0.05）。SLE患者外周血中表达CCR4的细胞百分比（20.24% ± 13.86%）较正常人对照组（10.44% ± 3.07%）升高（P < 0.01）,且CD3+CCR4+细胞百分比高于CD3-CCR4+细胞百分比。与正常人对照组比较,重度活动的SLE患者 CCL22水平降低（P ＜ 0.05）,SLE患者CCR4的表达水平随着SLEDAI评分的升高而升高。SLE患者CCL22与SLEDAI评分呈负相关（r = -0.308,P < 0.05）。结论 CCL22/CCR4在SLE发生、发展及器官损害中可能起一定的作用。     

CCL27、CCRl0在鲍温病患者皮损中的表达

目的：比较CCL27、CCR10在鲍温病患者皮损及正常皮肤中的表达水平,并分析其与鲍温病发病的联系.方法：采用免疫组化染色SABC法检测14例鲍温病患者组织和7例正常皮肤中CCL27、CCR10的表达.结果：鲍温病患者皮损中,CCL27、CCR10的表达水平明显高于正常皮肤（t=-4.34,P〈0.01;t=-12.32,P〈0.01）,CCL27 、CCR10的表达水平差别明显小于正常皮肤（t=4.20,P〈0.01）.结论：CCL27、CCR10在鲍温病患者皮损中的高表达可能与鲍温病发病密切相关.     

CCL27、CCR10在鲍温病患者皮损中的表达

目的:比较CCL27、CCR10在鲍温病患者皮损及正常皮肤中的表达水平,并分析其与鲍温病发病的联系。方法:采用免疫组化染色SABC法检测14例鲍温病患者组织和7例正常皮肤中CCL27、CCR10的表达。结果:鲍温病患者皮损中,CCL27、CCR10的表达水平明显高于正常皮肤(t=-4.34,P<0.01;t=-12.32,P<0.01),CCL27、CCR10的表达水平差别明显小于正常皮肤(t=4.20,P<0.01)。结论:CCL27、CCR10在鲍温病患者皮损中的高表达可能与鲍温病发病密切相关。     

嗜酸粒细胞活化趋化因子及其与某些皮肤病的关系

CC型趋化因子嗜酸粒细胞活化趋化因子因最初认为高度选择的趋化嗜酸粒细胞而命名，包括嗜酸粒细胞活化趋化因子-1、2、3，其主要受体为CCR3。嗜酸粒细胞活化趋化因子和受体结合后参与细胞趋化、炎症和组织损伤。研究显示，它们参与多种皮肤病的发病过程，包括自身免疫性大疱病、特应性皮炎、荨麻疹、色素失禁症和新生儿中毒性红斑。     

microRNA在炎症性皮肤病中作用的研究进展

【摘要】 microRNA（miRNA）是一类转录后调控基因表达的非编码RNA分子,参与皮肤各种病理生理过程。近年来,miRNA表达谱的变化已被报道与部分炎症性皮肤病相关,例如miR-203、miR-146a、miR-21在银屑病皮损中表达上调;miR-155、miR-146a在特应性皮炎皮损中表达上调;miR-21、miR-223、miR-142-3p、miR142-5p在过敏性接触性皮炎皮损表达上调;而miR-146a、miR-155在系统性红斑狼疮患者外周血表达下调;miR-223在皮肌炎皮损中表达下调等。本文综述miRNA与部分炎症性皮肤病发生、发展之间的联系。     

白细胞介素36α对小鼠银屑病样皮损及趋化因子CCL20的影响

目的 探讨白细胞介素(IL)36α对小鼠银屑病样皮损及CC趋化因子配体20(CCL20)的影响.方法 30只BALB/c雌性小鼠分为3组:凡士林空白对照组(对照组)、咪喹莫特模型组(模型组)以及IL-36α实验组(实验组).用小鼠银屑病皮损面积和疾病严重程度评分(PASI)观察银屑病样小鼠皮损动态变化.光镜下观察皮损组织形态学变化,并测量表皮层厚度.用实时荧光定量PCR、Western印迹检测对照组与模型组小鼠皮损中IL-36α表达情况,用实时荧光定量PCR、Western印迹法、免疫组化方法检测小鼠皮损中CCL20的含量变化.结果 模型组皮损中IL-36α mRNA表达水平明显高于对照组(△Ct值分别为0.0195±0.0059、0.0012±0.0004,两组比较,P＜0.05);模型组皮损中IL-36α蛋白表达水平明显高于对照组(分别为3.922±0.248、0.690±0.025,两组比较,P＜0.05).对照组、实验组CCL20 mRNA表达(△Ct值)分别为0.378±0.075、2.152±0.793,与模型组(0.999±0.178)比较,差异有统计学意义(P＜0.05);对照组、实验组CCL20蛋白表达结果分别为0.025±0.009、0.397±0.033,与模型组(0.145±0.030)比较,差异有统计学意义(P＜0.05).免疫组化结果表明,实验组皮损中CCL20的含量较模型组显著增加,差异有统计学意义(Z=2.294,P＜0.05).结论 IL-36α可通过促进CCL20表达,加重银屑病样小鼠皮损病变.     

蕈样肉芽肿患者瘙痒与趋化因子CCL17相关性研究

【摘要】 目的 寻找参与蕈样肉芽肿（MF）患者瘙痒发生的相关分子。方法 纳入2009年10月至2021年8月于北京大学第一医院就诊的522例MF患者作为研究对象,统计瘙痒发生率。根据是否有瘙痒症状对患者进行分组,分析其中49例患者皮损活检组织的RNA测序数据,寻找有瘙痒症状与无瘙痒症状患者的差异表达基因;使用酶联免疫吸附试验和免疫组织化学技术分别检测88例MF患者血清和81例MF患者组织CC趋化因子17（CCL17）蛋白表达量;使用流式细胞仪检测46例患者外周血T淋巴细胞活化和分化标记,寻找与瘙痒症状相关的外周血淋巴细胞亚群。使用χ2检验、Mann-Whitney U检验、Spearman相关性检验进行统计分析。结果 522例患者中,男305例,女217例;早期MF 347例,进展期MF 175例。MF患者瘙痒发生率为67.2%（351例）,进展期患者瘙痒发生率（81.7%,143/175）较早期患者（59.9%,208/347）上升（χ2 = 25.03,P＜0.001）。RNA测序结果显示,瘙痒MF患者CCL17 mRNA表达量高于无瘙痒MF患者（差异表达倍数 = 10.09,P＜0.001）。瘙痒患者血清CCL17浓度［1 017.05（377.12,4 831.80） pg/ml］较无瘙痒患者［361.66（180.47,500.08） pg/ml］上升（Z = -4.57,P＜0.001）,且与瘙痒评分呈正相关（r = 0.57,P = 0.010）。在早期和进展期MF患者中,瘙痒患者血清CCL17浓度均高于无瘙痒患者（Z = -3.68,P＜0.001;Z = -2.54,P = 0.011）。瘙痒患者与无瘙痒患者CCL17免疫组化相对定量评分差异无统计学意义（Z = -1.84,P = 0.066）。瘙痒患者CD3+CD4+CD26-CCR4+恶性T细胞百分比高于无瘙痒MF患者（Z = -2.03,P = 0.043）,且与血清CCL17浓度呈正相关（r = 0.49,P＜0.001）。结论 MF瘙痒患者皮损组织CCL17mRNA和血清CCL17浓度上升,CCL17与MF患者瘙痒发生相关,可能通过招募CD3+CD4+CD26-CCR4+恶性T细胞参与瘙痒发生。     

寻常性银屑病患者血清趋化因子CCL27的检测及临床意义

目的 检测寻常性银屑病患者血清CCL27水平并探讨其临床意义。方法 采用酶联免疫吸附法检测61例寻常性银屑病患者治疗前后和45例健康人血清CCL27水平。结果 61例寻常性银屑病患者血清CCL27水平为（670.02 ± 262.15） ng/L,健康人对照组为（373.10 ± 92.84） ng/L,两组差异有统计学意义（t ＝ 8.18,P ＜ 0.01）。进行期患者血清CCL27水平为（799.94 ± 214.54） ng/L,静止期为（422.57 ± 135.53） ng/L,两组差异有统计学意义（t ＝ 8.39,P ＜ 0.01）。经药物治疗8周后,银屑病患者PASI评分下降70％以上者36例,其CCL27水平明显下降,与治疗前比较,差异有统计学意义（t ＝ 9.95,P ＜ 0.01）;PASI评分下降不足70％者25例,CCL27水平与治疗前比较差异无统计学意义（t ＝ 1.84,P ＞ 0.05）。61例银屑病患者血清CCL27水平与PASI评分呈正相关（r ＝ 0.58,P ＜ 0.01）。结论 寻常性银屑病患者血清CCL27水平明显增高,并与疾病活动性相关。     

高迁移率族蛋白1在皮肤病中的作用

高迁移率族蛋白(HMGB)1是一种核蛋白、非组蛋白性的DNA结合蛋白。它可以存在于细胞核、细胞质和细胞外基质中,分别发挥不同的生理或病理作用。HMGB1可以结合DNA并作为一种基因转录的辅助因子,当其释放到细胞外基质中时,可作为损伤相关的分子模式(DAMP)产生促炎因子,通过激活多种细胞表面受体如糖基化终产物(RAGE)和Toll样受体(TLR),并且激活核因子(NF)-k B等信号通路来实现免疫应答和炎症反应。HMGB1也可以调节细胞自噬和凋亡。该文对由HMGB1介导的这些炎症和免疫作用在皮肤疾病中发挥的作用作一综述。     

内源性大麻素系统与炎症性皮肤病

内源性大麻素系统包括内源性大麻素受体和内源性大麻素以及一系列参与内源性大麻素系统生物合成和代谢的酶类以及膜转运受体.近年来,在角质形成细胞、皮肤成纤维细胞、皮脂腺细胞等多种皮肤细胞中发现了具有生物学效应的内源性大麻素系统.越来越多的研究发现,内源性大麻素系统参与正常皮肤生理生化活动和炎症反应,并在多种炎症性皮肤病中起作用.目前内源性大麻素系统的临床应用尚不成熟,但内源性大麻素系统的研究为临床炎症性皮肤病的治疗提供了新视角和新策略.     

维A酸的抗炎作用及在炎症性皮肤病中的应用

维A酸类药物通过与维A酸受体结合调节上皮细胞的增殖和分化,具有抗炎和免疫调节作用,在多种自身免疫炎症性疾病的治疗中起作用.维A酸通过影响中性粒细胞、单核/巨噬细胞、树突细胞、肥大细胞、T细胞和B细胞等免疫细胞和多种细胞因子参与机体的免疫防御和抗炎过程.维A酸用于治疗银屑病、痤疮、扁平苔藓等多种炎症性皮肤病获得良好疗效.     

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept

BACKGROUND: Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. OBJECTIVES: To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. METHODS: Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. RESULTS: All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the treatment. Skin histological abnormalities showed statistically significant modifications during treatment (P < 0.001). Immunohistochemical expression of CTACK/CCL27 decreased significantly (P < 0.001) and its relation with final PASI score was statistically significant (P < 0.05); the pattern of distribution of CTACK/CCL27 immunoreactivity significantly moved from diffuse and predominantly suprabasal to basal (P < 0.001) and the restoration of basal distribution of CTACK/CCL27 was also significantly related to clinical improvement of cutaneous disease (P < 0.001). CONCLUSIONS: Etanercept induces a clinical and histological improvement of psoriatic disease, promoting a reduction in CTACK/CCL27 cutaneous immunostaining and favouring the restoration of physiological CTACK/CCL27 epidermal expression. Moreover, CTACK/CCL27 reduction in cutaneous expression during administration of etanercept could be considered a favourable prognostic marker.     

Kinetics and differential expression of the skin-related chemokines CCL27 and CCL17 in psoriasis, atopic dermatitis and allergic contact dermatitis

CCL27 and CCL17 are chemokines believed to be involved in the process of establishing the inflammatory infiltrate, characteristic for the various inflammatory skin diseases. The skin-specific CCL27 binds the chemokine receptor-10 (CCR10), and CCL17 is a chemokine receptor-4 (CCR4) ligand. The purpose of our study was to characterize the expression of CCL27 and CCL17 in the inflammatory skin diseases: psoriasis, atopic dermatitis (AD) and acute allergic contact dermatitis (ACD) induced in nickel-sensitive individuals. Surprisingly, our studies revealed a markedly decreased CCL27 mRNA and protein expression in psoriatic lesions compared with non-lesional psoriatic skin. A minor CCL17 mRNA increase was measured in lesional psoriatic skin. No alterations were found in AD. In ACD, we found a pronounced (90-fold) raise in CCL17 mRNA and a 50-fold increase in CCL17 protein compared with normal skin. A kinetic ACD study of CCL17 expression showed the highest mean value 24 h after hapten application. Furthermore, we found the mRNA levels of CCR10 and CCR4 paralleling the results of their corresponding ligands. Overall, our principal findings were a distinct decrease in CCL27 in lesional psoriatic skin and a marked upregulation of CCL17 in ACD. These findings underscore the differential cutaneous T-cell recruitment in different inflammatory diseases.     

CCL27及其受体在银屑病血清和皮损中的表达

目的:检测趋化因子CCL27及其受体CCR10在银屑病患者血清和皮损中的表达.方法:采用ELISA方法检测40例银屑病患者血清CCL27水平,并采用免疫组化SP法检测其中25例患者皮损和15例正常人皮肤中CCL27和CCR10的表达情况.结果:(1)银屑病患者血清CCL27水平(799.94±214.54)pg/mL,高于健康人对照组(373.10±92.84)pg/mL,P<0.001.(2)在寻常型银屑病患者皮损,CCL27强烈表达于皮肤基底层至颗粒层,CCR10表达于真皮浅层淋巴细胞,表达阳性率明显高于正常人皮肤(P<0.001).结论:CCL27与受体CCR10相互作用,参与了银屑病的发病.     

Optimal use of topical corticosteroids in inflammatory skin diseases

The optimal use of topical corticosteroids (TC) in the treatment of inflammatory disorders of the skin is related to a number of factors concerning the drug on the one hand (potency, pharmacological properties, formulation), and the patient on the other hand (type and phase of the disease, characteristics of the lesion, site to be treated, age and general conditions). The careful balance between drug and disease/patient allows the establishment of a simple series of gold standard guidelines for TC treatment.     

Helicobacter pylori and inflammatory skin diseases

Throughout the history of mankind, infections have been the major cause of diseases. Over the last decades, not only the incidence of emerging infectious diseases have increased, but also tremendous strides have been made in understanding the biology of several pathogenic microorganisms. Helicobacter pylori(H. pylori) is a spiral-shaped, gram-negative bacterium, which infects over the half of the world's population. H. pylori has been implicated in the pathogenesis of a number of gastrointestinal disorders. However, new researches have demonstrated that H. pylori is also involved in the pathogenesis of various extragastric diseases. The difference in the clinical outcome of H. pylori infection may be explained, at least in part, by host response to the infection and H. pylori virulence factors. It is obvious that as developments in the research on H. pylori spring up, an understanding of the pathophysiology of H. pylori infection will continue to be identified. Here in this review, we summarize the current knowledge about H. pylori and its association with inflammatory skin diseases.     

白细胞介素22对人表皮角质形成细胞CC趋化因子配体27表达的影响

目的 研究白细胞介素22（IL-22）对人表皮角质形成细胞CC趋化因子配体27（CCL27）表达的影响及机制。方法 免疫组化法检测10例银屑病患者皮损及5例健康对照组皮肤中CCL27的表达。培养HaCaT细胞,分为8组：对照组用PBS处理,IL-22处理组分别用12.5、25、50、100、200 μg/L IL-22处理,信号通路阻断组先分别加入50 μmol/L AG490（JAK2/STAT3通路抑制剂）或PD98059（MAPK-ERK1/2通路抑制剂）阻断处理,2 h后各加入50 μg/L IL-22,继续于37 ℃、5% CO2孵箱中培养。孵育24 h 后,分别提取 HaCaT 细胞总蛋白并收集上清液,Western印迹、ELISA法分别检测CCL27表达。结果 免疫组化检测示,银屑病患者皮损中CCL27的表达水平明显高于正常人皮肤。Western 印迹显示,HaCaT细胞分别用12.5、25、50、100、200 μg/L IL-22处理后,CCL27相对表达量逐渐升高至0.491 ± 0.013、0.620 ± 0.019、0.623 ± 0.014、0.802 ± 0.052、1.138 ± 0.013,均较对照组（0.413 ± 0.013）升高（P＜0.01）;IL-22 + AG490组及IL-22 + PD98059组CCL27表达量分别为0.411 ± 0.019和0.280 ± 0.012,均低于50 μg/L IL-22组（均P＜0.01）。ELISA法检测显示,各组HaCaT细胞CCL27分泌水平变化趋势与Western印迹法检测结果一致。结论 IL-22可促进HaCaT 细胞CCL27表达,其机制可能与MAPK-ERK1/2和JAK2/STAT3通路有关。