寻常型银屑病患者及正常人S100A6、S100A8、S100A9基因的研究

目的：通过测定家族性寻常型银屑病患者和正常人中S100A6、S100A8和S100A9基因的外显子编码区序列，探索其与银屑病发病的关系。方法：从家族性寻常型银屑病患者和正常人的外周血中提取基因组DNA，用自动测序法测定S100A6、S100A8和S100A9基因的外显子编码区序列。结果：患者和正常对照组的S100A6、S100A8、S100A9基因外显子编码区序列均相同，未发现基因多态性。结论：S100A6、S100A8、S100A9基因的外显子编码区序列与家族性寻常型银屑病发病无相关性。     

白介素-8单克隆抗体乳膏治疗寻常型银屑病

根据白细胞介素-8（IL-8）在银屑病发病中所起的作用，抗人IL-8单克隆抗体乳膏为银屑病的治疗开辟了一条新途径，我们于2002年1～12月对其治疗寻常型银屑病进行了观察。     

寻常型银屑病患者血清白介素-2水平测定

2000年10月～2001年10月笔者采用ELISA方法检测了30例寻常型银屑病患者血清中白介素-2(IL-2)的浓度,并进行了银屑病面积和严重程度指数(PASI)评分,了解两者之间的相关性,进一步探讨银屑病的发病机制。病例组:30例寻常型银屑病患者均来自笔者所在科室门诊,排除相关疾病及各种影响因素。其中男14例,女16例,平均年龄(28.23±12.60)岁(9～60岁)。平均病程(32.81±50.63)个月(20d～16年)。对照组:20例,男8例,女12例;平均年龄(30.10±10.00)岁(17～45岁)。经t检验,性别、年龄差异无显著性。ELISA检测严格按照IL-2试剂盒(深圳晶美公司)说明…     

基质金属蛋白酶-8在寻常型银屑病患者血清及皮损中的表达研究

 目的:探究基质金属蛋白酶-8（MMP-8）在寻常型银屑病（PV）炎症反应中的作用。方法:将20例PV患者根据银屑病面积和严重程度指数（PASI）分为轻度组6例、中度组6例及重度组8例。用ELISA法检测并比较PV患者组及正常对照组(12例)血清中MMP-8浓度;用荧光定量PCR扩增并比较不同病情严重程度组间皮损处以及外观正常的周边皮肤MMP-8相对表达量;用免疫组化法观察MMP-8在皮损部位的分布状况。结果:血清MMP-8浓度比较：轻度组明显低于对照组(t=2.54,P=0.022）、重度组（t=2.69,P=0.020）。PV患者皮损部位MMP-8表达明显高于皮损相邻部位外观正常的皮肤（t=2.91,P=0.009）;重度组PV皮损部位MMP-8表达明显高于轻度组（t=3.45,P=0.005）及中度组（t=2.74,P=0.018）。在PV皮损部位,MMP-8主要表达于表皮基底细胞及棘细胞,而在皮损周边部位,MMP-8在基底细胞中表达较明显。真皮中MMP-8主要表达于小血管处。结论:MMP-8在炎症反应较强的皮损中表达上升,推测其通过调控炎症反应及促进血管新生等参与PV的免疫病理进程。     

抗人白介素8单克隆抗体乳膏治疗寻常型银屑病多中心临床试验

银屑病是一种原因不明的慢性炎症性疾病,多种细胞因子和炎症介质,如白介素8等在银屑病发病机制中起重要作用.加拿大YES生物技术研究有限公司研制了抗人白介素8单克隆抗体乳膏(简称IL-8单抗乳膏,45μg/g)外用治疗银屑病.1999年10月至2000年6月,我们对该药进行Ⅱ、Ⅲ期临床研究.     

寻常型银屑病皮损肥大细胞密度及IL-8表达的研究

目的：探讨肥大细胞和IL-8在寻常型银屑病中的作用。方法：采用免疫组化技术(SABC法)观察寻常型银屑病皮损处MC分布和IL-8在表皮中的表达情况。结果：寻常型银屑病皮损处MC密度明显高于皮肤血管炎组和健康对照组；寻常型银屑病皮损处KC中IL-8的表达明显高于两对照组。结论：结果提示MC和IL-8参与寻常型银屑病的致病过程，并且两者之间存在相关性。     

抗人白介素-8单克隆抗体乳膏治疗寻常型银屑病临床观察

根据IL-8在银屑病发生中的重要作用，加拿大YES生物技术研究有限公司研制了抗人白介素-8单克隆抗体乳膏(45ug／g)外用治疗银屑病。2001年8月～2002年8月作者对IL-8单抗乳膏治疗寻常型银屑病的疗效、安全性进行开放性临床试验。     

脓疱性银屑病患者外周血IL-8水平及其在皮损中的表达

许多学者发现,IL-8与银屑病发病有密切关系,脓疱性银屑病皮损中有比寻常性银屑病皮损中更多的中性粒细胞浸润和IL-8持续升高.2004年7月至2006年2月,我们采用双抗体夹心法及免疫组化技术检测脓疱性银屑病、寻常性银屑病及正常人对照组外周血IL-8水平及皮损处IL-8的表达情况.     

寻常型银屑病患者血清S100A13的检测及意义

目的:检测寻常型银屑病患者血清钙结合蛋白S100A13水平.方法:酶联免疫吸附法(ELISA)测定寻常型银屑病患者和健康人群血清S100A13水平.结果:轻症20例寻常型银屑病患者组血清水平为(66.172±22.076)μg/L,重症20例寻常型银屑病患者组为(168.492±101.127)μg/L,正常对照组血清水平为(40.075±10.338)μg/L,组间差异有统计学意义(P＜0.01).结论:寻常型银屑病皮损的过度增殖和异常分化可能与S100A13的大量上调及分泌有关.     

Dectin-1 mRNA在寻常型银屑病患者皮损中的表达

目的检测寻常型银屑病患者皮损组织中dectin-1 mRNA的表达,探讨dectin-1在银屑病发病中的可能机制。方法采用实时荧光定量聚合酶链反应(RFQ-PCR)检测15例寻常型银屑病患者皮损组织及15例正常皮肤组织中dectin-1 mRNA的表达。结果寻常型银屑病患者皮损中dectin-1 mRNA的表达为(0.01020±0.00686),较正常皮肤组织(0.00232±0.00073)明显升高,差异有统计学意义(P0.05)。结论 Dectin-1 mRNA表达水平在寻常型银屑病患者皮损中明显升高,其可能在寻常型银屑病患者皮肤局部免疫反应中起作用。     

Comparison of the Expression Profile of JunB, c-Jun, and S100A8 (Calgranulin A) in Psoriasis Vulgaris and Guttate Psoriasis

Background

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. Recently, several psoriasis-linked genetic loci have been reported; PSORS4 contains S100A8 (calgranulin A), and PSOR6 (19p13) locus harbors JunB (19p13.2). S100A8 is considered to be a marker of inflammation in a variety of diseases. The expression of JunB and c-Jun have been reported to be reduced in psoriatic lesions.

Objective

We attempted to assess the role and correlation of S100A8, JunB, and c-Jun in the pathogenesis of guttate psoriasis and psoriasis vulgaris by studying whether any difference of immunohistochemical expression existed.

Methods

Skin biopsy specimens from patients with psoriasis vulgaris (n=37) and guttate psoriasis (n=17), and a normal skin controls (n=9) were utilized in the study. Formalin-fixed and paraffin-embedded tissue sections were prepared and JunB, c-Jun, and calgranulin A were immunohistochemically stained in order to compare the expression of those three proteins in each group.

Results

Reduced JunB expression was observed in patients with psoriasis vulgaris and guttate psoriasis, as compared to patients in the control group; however, c-Jun expression was reduced only in the psoriasis vulgaris group. The expression of S100A8 increased in the psoriasis groups as compared to the control group. In addition, the expression of S100A8 was different between the psoriasis vulgaris and guttate psoriasis groups; S100A8 was expressed more profoundly in the guttate psoriasis group (p<0.05).

Conclusion

Our results indicate that S100A8 contributes to the pathogenesis of guttate psoriasis, and it may be a good target for therapy for guttate psoriasis provoked by microorganisms.     

Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis

BACKGROUND: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. OBJECTIVES: We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. METHODS: Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. RESULTS: A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705+/-120 ng mL-1 (mean+/-SEM, n=18), those with a PASI of >or=15 showed levels of 1315+/-150 ng mL-1 (n=32) while controls presented with 365+/-50 ng mL-1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. CONCLUSIONS: Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions.     

DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis

S100A9 and S100A8 are called damage‐associated molecular pattern (DAMP) molecules because of their pro‐inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house‐dust mites affect S100A9 and S100A8 expression in Th2 cytokine‐ and Th17 cytokine‐treated keratinocytes, and how secretion of these molecules affects keratinocyte‐derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL‐17A‐ and Dermatophagoides (D.) farinae‐treated keratinocytes, respectively. Furthermore, co‐treatment with D. farinae and IL‐17A strongly increased expression of S100A9 and S100A8 compared with D. farinae‐Th2 cytokine co‐treatment. The IL‐33 mRNA level increased in a dose‐dependent manner in S100A9‐treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP‐mediated inflammation in AD triggered by IL‐17A and house‐dust mites.     

S100A4蛋白和上皮钙黏蛋白-E在黑素瘤中的表达及意义

目的探讨黑素瘤的发生和侵袭转移机制,检测S100A4蛋白、上皮钙黏蛋白-E(E-cadherin)在黑素瘤的表达水平。方法应用免疫组织化学SP法检测30例黑素瘤、30例黑素细胞痣和20例正常皮肤组织中S100A4和E-cadherin蛋白的表达。结果 S100A4在黑素瘤组织中表达的阳性率为66.67%,明显高于其在黑素细胞痣中的表达(13.33%),在正常皮肤组织中基本不表达,两者比较差异有统计学意义(P0.05);E-cadherin在正常皮肤组织表达率为100%,与在黑素细胞痣中的表达(83.3%)差异无统计学意义,在黑素瘤组织中表达率为43.33%,与正常皮肤组织比较有统计学意义(P0.05)。在有淋巴转移和无淋巴转移的黑素瘤中S100A4和E-cadherin的表达差异均有统计学意义(P0.05)。结论 S100A4和E-cadherin与黑素瘤的转移可能有关,提示黑素瘤组织中S100A4和E-cadherin的检测可作为预测肿瘤转移的指标之一。     

Detection of psoriasin/S100A7 in the sera of patients with psoriasis

Background  Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein.
Objectives  To determine if patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies.
Methods  Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides.
Results  We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL⁻¹) than in controls (mean 331 ng mL⁻¹, P  =   0·308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean 0·347 vs. 0·255 units, P  =   0·246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity.
Conclusions  Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical psoriasis.     

Anti-apoptotic role of S100A8 in X-ray irradiated keratinocytes

BACKGROUND: Ionizing radiation is used to treat a lot of cancers, however, it also produced unwanted side effect on normal tissues, such as radiodermatitis. We previously established an animal model for radiodermatitis, and identified many of radiation-induced genes by cDNA microarray. Of the candidates, we chose S100A8 gene for a further study. OBJECTIVE: The aim of this study is to investigate the functional role of S100A8 in X-ray irradiated keratinocytes. METHODS: RT-PCR and immunohistochemistry were performed to demonstrate the S100A8 induction by X-ray irradiation. HaCaT keratinocytes were transduced with the recombinant adenovirus expressing GFP-S100A8, and then effects on cell cycle and apoptosis were analyzed using flow cytometry and Western blot. RESULTS: X-ray irradiation markedly induced S100A8 expression in the hyperplastic epidermis of mouse. Overexpression of S100A8 by adenoviral transduction led to the enhancement of cell proliferation in the absence and/or presence of X-ray irradiation, as compared with Ad/GFP control group. Furthermore, overexpression of S100A8 significantly protected the X-ray-induced apoptosis. CONCLUSION: These results suggest that S100A8 have an anti-apoptotic role in X-ray irradiated keratinocytes.     

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation

BackgroundS100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established.ObjectiveThis study aims to investigate the relationship between S100A8 and cutaneous SCC development.MethodsWe performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation.ResultsS100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity.ConclusionS100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin.     

寻常型银屑病患者趋化因子受体7表达及其意义探讨

目的探讨趋化因子受体家族中CC趋化因子受体7(CCR7)在寻常型银屑病患者皮损及外周血T细胞上的表达情况。方法应用免疫组化和流式细胞分析的方法分别检测23例寻常型银屑病患者皮损和外周血T细胞表面CCR7的表达。结果与正常人皮肤相比,寻常型银屑病患者皮损中CCR7表达明显增高(P<0.01);通过流式细胞分析发现患者外周血T细胞表面CCR7表达也同样高于正常对照(P<0.01)。结论寻常型银屑病患者皮损和外周血中CCR7+记忆性淋巴细胞数量及分布异常可能与疾病的炎症维持密切相关。