HB-EGF在进行期银屑病皮损中的表达

目的　探讨肝素结合表皮生长因子样生长因子 (HB EGF)在银屑病发病早期中的作用机制。方法　用免疫组织化学的方法检测正常皮肤组织、银屑病未受累皮肤和进行期银屑病皮损中HB EGF的表达。结果　正常皮肤中 ,HB EGF位于基底层 ( 10 0 % ) ,基底上层几乎不表达 ;在银屑病未受累皮肤和银屑病皮损的周围部分中 ,HB EGF表达升高 ,不仅位于基底层 ,且以灶状分布于基底上层 ( 95 .2 4% ,85 .71% ) ;在银屑病皮损的中央部分 ,全层均无HB EGF表达。结论　HB EGF在银屑病发病的早期阶段可能起一定作用 ,纠正其异常表达可能为银屑病治疗开辟新途径 ,提供新药物。     

外用维甲酸对表皮生长因子受体表达作用的研究

目的：了解维甲酸外用前后表皮生长因子受体的分布，以便有助于进一步探讨维甲酸治疗银屑病的机理。方法：应用免疫组化技术，观察分析正常人正常皮肤、0．1％维甲酸乳膏外用4天后表皮生长因子受体的分布，并与银屑病皮损及未受累皮肤作对照。结果：正常皮肤中表皮生长因子受体间断性“串珠样”分布于基底层及基底上层，外用维甲酸后阳性细胞数显著增加，失去“串珠样”特征。银屑病皮损中表皮生长因子受体遍布表皮全层，在基底层呈连续性分布，而在未受累皮肤，阳性细胞数明显减少。结论：外用维甲酸可增强表皮生长因子受体的表达，这种增强是否是对银屑病表皮生长因子过度表达的负反馈抑制需进一步研究。     

银屑病患者皮损表皮生长因子及其受体的检测

用抗表皮生长因子（ＥＧＦ）多克隆抗体、抗表皮生长因子受体（ＥＧＦＲ）单克隆抗体及ＡＢＣ免 疫酶标技术，对２０例寻常型银屑病患者皮损及１０例正常人皮肤进行观察。结果表明：①正常人皮肤及 银屑病非皮损区皮肤ＥＧＦ及ＥＧＦＲ主要分布在表皮基底细胞层及基底层上部。②银屑病进行期皮损 ＥＧＦ及ＥＧＦＲ分布于表皮各层，表皮中、上层含量明显升高。③经有效治疗消退期皮损ＥＧＦ及ＥＧＦＲ 从角质层开始消退，分布趋于正常。提示ＥＧＦ及ＥＧＦＲ对银屑病皮损角肮细胞过度增殖及异常分化起 重要作用。     

维甲酸诱导前后HB-EGF在银屑病皮损中的变化

目的　研究维甲酸在进行期寻常型银屑病中的治疗机制。方法　用免疫组织化学的方法检测维甲酸诱导前后HB GFE在进行期银屑病皮损中的表达。结果　在银屑病皮损中 ,全层几乎无HB EGF的表达 ,维甲酸诱导后 10天可见HB EGF不仅表达于基底层 (10 0 .0 % ) ,且以灶状表达于基底上层 (77.8% )。结论　维甲酸通过上调银屑病表皮中HB EGF的表达 ,抑制角质形成细胞的增殖并诱导凋亡     

表皮生长因子受体在寻常性银屑病表皮中的表达

应用鼠抗人表皮生长因子受体的单克隆抗体，以ＡＢＣ免疫组化法对３０例寻常性银屑病患者及２０例正常人表皮中表皮生长因子受体进行检测。结果显示：ＥＧＦ－Ｒ在正常人主要分布于基底细胞层，棘细胞层以上显著减少至消失。而寻常性银屑病皮损的表皮ＥＧＦ－Ｒ除基底层与正常人相似外，棘细胞以上各层显著增加。提示ＥＧＦ－Ｒ可能在银屑病表皮的过度增殖及基底上层角朊细胞的异常分化中起着直接的作用。     

IL－15 mRNA在寻常型银屑病皮损中的表达

@@@@目的：检测IL－15 mRNA在寻常型银屑病（PV）皮损中的表达。方法：采用原位杂交方法检测35例寻常型银屑病患者皮损及20例正常人表皮IL－15 mRNA的表达。结果：在正常皮肤组织中IL－15 mRNA表皮基底层阳性着色3例，阳性率15．0％，阴性着色17例；在PV皮损组织中，IL－15 mRNA主要在表皮基底层形成细胞胞浆阳性着色，阳性率100％，强阳性为57．1％（20？35），中强阳性为31．4％（4？35），阳性为11．4％（4？35），两组间有显著性差异。在PV皮损组织中IL－15 mRNA表达线性密度为9．512±6．503，高于在正常皮肤组织中的表达（1．339±1．011），差异有统计学意义。结论：IL－15 mRNA在PV的发病过程中有显著的作用，为阐明PV的发病机制及病变的演变过程提出了新的理论依据。     

红斑、丘疹及鳞屑性皮肤病

980840 银屑病患者皮损及尿液中表皮生长因子及其受体的检测/王万卷（西安医大二院皮肤科）…//西安医科大学学报.-1997,18（3）.-379～380,385 应用鼠抗人表皮生长因子（EGF）受体单克隆抗体及~125Ih EGF放射免疫分析药盒,以放免分析法及ABC免疫组化法对30例寻常性银屑病患者及20例正常人皮肤及尿液中EGF及EGFR进行了检测。结果显示:（1）正常人皮肤EGFR主要分布于基底细胞层及基底层上部。（2）银屑病进行期皮损EGFR持续表达于表皮各层,其表皮中EGF含量显著高于正常人及银屑病邻近未受累表皮及恢复期表皮。（3）银屑病患者尿液中EGF在银屑病各期及正常人之间比较均无显著性差异。提示:EGF及EGFR可能在银屑病表皮的过度增殖及异常分化中起重要作用。表2参7 （沈子伟）980841 1121例银屑病患者小脓疱发生的分析/邓丙戌（北京中医医院皮肤科）…//临床皮肤科杂志.-1997,26（5）.-304～305     

bFGF及其mRNA在银屑病皮损的表达

目的探讨碱性成纤维细胞生长因子(bFGF)在银屑病发病机制中的作用。方法采用组织切片免疫组化和原位杂交技术对22例银屑病皮损和19例正常皮肤的bFGF进行检测。结果寻常型进行期银屑病皮损表皮bF-GF蛋白和mRNA阳性主要表达于表皮基底层和棘层,定位于细胞核、细胞浆和细胞膜;正常皮肤则表达于表皮的基底层,定位于细胞核、细胞浆和细胞膜。统计学分析发现银屑病皮损区表皮与正常皮肤表皮bFGF蛋白和mRNA均有显著性差异(P<0.01)。结论bFGF可能参与银屑病角质形成细胞增殖和真皮微血管异常的发生。     

银屑病皮损c－erbB－1及c－erbB－2原癌基因表达及其意义

用抗ｃ－ｅｒｂＢ－１（ＥＧＦＲ）及ｃ－ｅｒｂＢ－２（Ｎｅｕ蛋白）原癌基因表达蛋白单抗及免疫组化技术，观察２０例银屑病皮损及１０例正常人皮肤。结果表明：（１）在正常人皮肤表皮中，ＥＧＦＲ基因表达蛋白主要分布在基底细胞层，Ｎｅｕ蛋白表达蛋白主要分布在棘层上部及颗粒细胞层。（２）银屑病活动性皮损表皮棘层及颗粒层ＥＧＦＲ表达增强，而Ｎｅｕ蛋白表达减弱。银屑病皮损表皮两种原癌基因表达异常对皮损形成可能起一定作用。     

DNA结合蛋白A在银屑病皮损中的表达

目的研究DNA结合蛋白A(DBPA)在银屑病皮损中的表达及其与表皮角质形成细胞分化的关系。方法采用免疫组化和原位杂交的方法检测正常皮肤组织、未受累组织和银屑病皮损中DBPA蛋白和mRNA的表达变化。结果 DBPA蛋白和mRNA强表达于正常组织表皮颗粒层,弱表达于棘层上部;在未受累组织中强表达于颗粒层及棘层上部;在银屑病皮损中,DBPA表达于除基底层的表皮全层。结论 DBPA可能参与银屑病角质形成细胞的分化和增生。     

Alteration and significance of heparin-binding epidermal-growth-factor-like growth factor in psoriatic epidermis

BACKGROUND: Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has proved to be a mitogen of keratinocytes, which may be involved in the pathogenesis of inflammatory diseases, but its mechanism in psoriasis remains unknown. OBJECTIVE: To investigate the alteration of HB-EGF in the epidermis of active psoriasis vulgaris. METHODS: The expression of HB-EGF in normal skin tissues, uninvolved tissues and psoriatic lesions was detected by in situ hybridization and immunohistochemistry. RESULTS: HB-EGF mRNA and protein were located in the basal layer of normal epidermis (10/10, 100.00%), with nearly no expression in the suprabasal layers (1/10, 10.00%); the expression of HB-EGF was located not only in the basal layer (21/21, 100.00%), but was also seen as focal overexpression in the suprabasal layers of uninvolved epidermis (20/21, 95.24%) and the marginal part of psoriatic lesions (18/21, 85.71%), while nearly no expression of HB-EGF was found in the central part of psoriatic lesions (1/21, 4.76%). CONCLUSION: HB-EGF may play an important role in the early pathogenesis of psoriasis.     

早幼粒细胞白血病基因及其蛋白在银屑病表皮中的表达

目的探讨早幼粒细胞白血病(PML)基因及其蛋白在银屑病发病中的作用机制。方法用原位杂交和免疫组化方法检测正常组织、进行期银屑病皮损及非皮损区PMLmRNA和蛋白表达。结果在正常人皮肤组织中,PMLmRNA和蛋白不表达(阴性);在非皮损区,PMLmRNA和蛋白在基底层和基底上层细胞核内低表达(52%,36%);在银屑病皮损周边PMLmRNA和蛋白在基底层和基底上层细胞核内呈灶状表达(72%,64%);在银屑病皮损中心表皮中,PMLmRNA和蛋白高表达(96%,88%)。结论PML基因和其蛋白在银屑病表皮中的过表达提示,PML基因可能与银屑病表皮细胞的过度增殖相关。     

K16 expression in uninvolved psoriatic skin: a possible marker of pre-clinical psoriasis

BACKGROUND: K16, a type I keratin, is upregulated in hyperproliferative states including psoriasis. It has been used as a marker of psoriasis and its expression is upregulated in relapsing psoriasis and downregulating in resolving. We evaluated non-lesional psoriatic skin for K16 expression. METHODS: Sixty-seven non-lesional and lesional skin samples from patients with psoriasis and normal skin from 19 non-psoriatic patients were studied by immunohistochemistry on frozen sections with K16. RESULTS: Seventeen of 19 normal skin samples showed staining of basal cells in the deeper part of the rete ridges. Sixty-two non-lesional psoriatic skin samples showed intense basal staining of K16. Of the remaining five non-lesional samples, diffuse intense suprabasal staining in one, pan-epidermal staining in two, and no staining was seen in two samples. Suprabasal (37), diffuse (14), sandwich (12), and basal (3) pattern staining were seen in psoriatic skin. One psoriatic skin sample did not show any expression. CONCLUSION: Our results demonstrate that K16 expression is also observed in non-lesional psoriatic skin and may serve as a marker of preclinical psoriasis.     

Immunofluorescence localization of nuclear retinoid receptors in psoriasis versus normal human skin

Psoriasis responds favourably to treatment with retinoids but the cellular pathways mediating these effects are poorly understood. Retinoids regulate keratinocyte proliferation and maturation via binding to nuclear retinoic acid receptors (mainly RARalpha and RARgamma) which form heterodimers with the 9-cis-RA receptor, RXRalpha. We have previously shown that mRNA expression of RARalpha and RXRalpha is down-regulated in psoriatic lesions as compared with non-lesional human skin. In the present study, we investigated the protein expression of RARalpha, RARgamma and RXRalpha in normal and psoriatic skin using indirect immunofluorescence analysis. Epidermal keratinocytes of normal and non-lesional psoriatic skin displayed similar nuclear localization of all three receptors; RARalpha was detected with decreasing intensity from basal to suprabasal layers, RARgamma showed the opposite trend, whereas RXRalpha was evenly expressed throughout the epidermis. In lesional psoriatic skin, however, all three receptor proteins showed a much higher staining intensity in the lower half of the epidermis; in particular, RARalpha immunoreactivity was low or even absent in the upper layers of epidermis. The results support the idea that psoriasis is associated with abnormal retinoid signalling in lesional epidermis.     

寻常性银屑病皮损及非皮损中IL-23(p19/p40)和IL-12(p35/p40)mRNA的表达

目的检测寻常性银屑病患者皮损及非皮损处IL-23(p19/p40)和IL-12(p35/p40)mRNA表达,探讨其临床意义。方法采用逆转录-聚合酶链反应(RT-PCR)检测寻常性银屑病患者皮损、非皮损处及正常人皮肤中IL-23(p19/p40)和IL-12(p35/p40)mRNA的表达水平。结果寻常性银屑病患者皮损中IL-23p19及p40(IL-23/IL-12)mRNA的表达均高于非皮损组织和正常皮肤组织(P<0.05),且非皮损处高于正常对照组,差异有显著性(P<0.05);IL-12p35mRNA在银屑病皮损处、非皮损处和正常对照中表达水平差异无显著性(P>0.05)。结论在寻常性银屑病发病过程中,IL-23可能发挥较IL-12更重要的作用。     

Hsp72 antigen expression in the proliferative compartment of involved psoriatic epidermis

Oxidative damage to growth regulatory proteins has been implicated in the aetiology of psoriasis. However, the transient synthesis of heat shock proteins has been shown to protect cells against the adverse effects of oxidative and other forms of physiological stress. This study has used an hsp72 monoclonal antibody to measure inducible 72 kDa heat shock protein expression in heat stressed normal human skin and established plaque psoriasis. Hsp72 was detected in the basal and suprabasal layer cells of heat-stressed normal skin, and in 12 involved psoriasis lesions. Hsp72 expression was not detected in unstressed normal skin or in 12 cases of uninvolved psoriasis. Immunoprecipitation and Western blotting of cell lysates from heat stressed normal skin and involved psoriasis lesions confirmed the presence of a 72 kDa polypeptide with hsp72 immunoreactivity. The MIB-1 monoclonal antibody was used to determine the proliferative fraction of normal and involved psoriastic epidermis. The Ki67 antigen was localised to the nuclei of basal and suprabasal layer cells of normal and involved psoriatic epidermis. Involved psoriatic epidermis contained a higher number of proliferating keratinocytes when compared with normal skin. The study has also demonstrated a strong correlation between hsp72 expression and keratinocyte proliferation in involved psoriatic epidermis (r=0.864, p<0.001). We believe that the 72 kDa inducible heat shock protein performs a protective function in the proliferative compartment of normal and involved psoriatic skin.