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例奶悄病上骸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地及颗粒层ＥＧＦＲ表达增强，而Ｎｅｕ蛋白表皮两种原癌基因表达异常对皮损形成可能起一定作用。     

c—erbB原癌基因与银屑病

为了探讨ｃ－ｅｒｂＢ与银屑病的关系，采用原位杂交的方法检测ｃ－ｅｒｂＢ－１原癌基因在正常人表皮和银屑病患者损皮中的表达，并观察了正常人朊细胞与银屑病患者ＩｇＧ和中血单一核细胞作用后ｃ－ｅｒｂＢ－１的表达。     

银屑病皮损区IL—8,HLA—DR,PLA2,ANAE,EGFR mRNA,c—fos mRNA的 …

目的 探讨银屑病患者白介素８（ＩＬ－８）,人类白细胞抗原ＤＲ（ＨＬＡ－ＤＲ）,磷脂酶Ａ２（ＰＬＡ２）,酸性α－乙酸萘酯酶（ＡＮＡＥ）,表皮生长因子受体基因（ＥＧＦＲｍＲＮＡ）,ｃ－ｆｏｓ基因（ｃ－ｆｏｓｍＲＮＡ）在皮损的表达定位。方法 对２０例银屑病患者皮损和１０例正常人的皮肤标本进行了免疫组化,组化和原位要交技术检测,结果 ＩＬ－８免疫反应于主要定位于表皮的基层,棘细胞层和颗粒层,血管内皮细胞及     

EGF－R PCNA及P53基因在银屑病皮损中的表达

用ＥＧＦ－Ｒ、ＰＣＮＡ及Ｐ５３抗体和ＬＢＳＡ方法观察了４３例寻常性银屑病患者表皮及１２例正常皮肤。结果发现ＥＧＦ－Ｒ及ＰＣＮＡ表达明显增强，除基底层细胞外，棘层及颗粒层也有明显表达，个别病例角质层仍有少量表达。提示银屑病患者皮损处细胞增殖及分化调控紊乱。还发现银屑病患者皮损及皮损周未受累皮肤中无Ｐ５３的表达。     

EGF－R PCNA及P53基因在银屑病皮损中的表达

用ＥＧＦ－Ｒ、ＰＣＮＡ及Ｐ５３抗体和ＬＢＳＡ方法观察了４３例寻常性银屑病患者表皮及１２例正常皮肤。结果发现ＥＧＦ－Ｒ及ＰＣＮＡ表达明显增强，除基底层细胞外，棘层及颗粒层也有明显表达，个别病例角质层仍有少量表达。提示银屑病患者皮损处细胞增殖及分化调控紊乱。还发现银屑病患者皮损及皮损周未受累皮肤中无Ｐ５３的表达。     

银屑病患者皮损纤维连接蛋白(FN)及转化生长因子-β_1(TGF-β_1)免疫组化观察

用免疫组化的方法观察１２例银屑病患者皮损及１２例正常人皮肤纤维连接蛋白（ＦＮ）、转化生长因子－β１（ＴＧＦ－β１）的表达和分布。结果表明，正常人皮肤ＦＮ呈线状分布于基底膜，表皮ＦＮ、ＴＧＦ－β１全部阴性。银屑病皮损表皮细胞间或细胞内ＦＮ染色阳性，呈网状或柱状排列；ＦＮ在表皮突明显缺损，其两侧增厚；ＴＧＦ－β１在颗粒层和棘层有染色。提示银屑病皮损ＦＮ和ＴＧＦ－β１异常表达，可能与银屑病免疫病理改变有关。     

银屑病患者皮损纤维连接蛋白（FN）及转化生长因子—β1（TGF—β1…

用免疫组化的方法观察１２例银屑病患者皮损及１２例正常人皮肤纤维连接蛋白（ＦＮ）、转化生长因子－β１（ＴＧＦ－β１）的表达和分布。结果表明，正常人皮肤ＦＮ呈线状分布于基底膜，表皮ＦＮ、ＴＧＦ－β１全部阴性。银屑病皮损表皮细胞间或细胞内ＦＮ染色阳性，呈网状或柱状排列；ＦＮ在表皮突明显缺损，其两侧增厚；ＴＧＦ－β１在颗粒层和棘层有染色。提示银屑病皮损ＦＮ和ＴＧＦ－β１异常表达，可能与银屑病免疫病理改变有     

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。     

表皮生长因子和原癌基因c－myc在银屑病皮损中的异常表达

表皮生长因子是强有力的促角朊细胞分裂剂，可以诱导原癌基因ｃ－ｍｙｃ的表达，而ｃ－ｍｙｃ又是调控细胞增殖的主要基因。应用免疫组化ＳＰ法对３０例银屑病和１２例正常对照组中的表皮生长因子和ｃ－ｍｙｃ的表达进行研究。结果显示ＥＧＦ和ｃ－ｍｙｃ在银屑病皮损中的异常表达，与正常人相比经统计学处理有显著性差异；银屑病皮损的严重程度与角朊细胞中ＥＧＦ和ｃ－ｍｙｃ和表达水平有明显相关性。     

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。     

c—Ha—ras原癌基因与银屑病

ｒａｓ癌基因与角朊细胞增殖、分化密切相关。本研究旨在利用斑点杂交和原位杂交法研究ｃ－Ｈａ－ｒａｓ癌基因在正常皮肤及进行期斑块型银屑病皮损中的表达，从癌基因角度初步探讨银屑病的发病机理。结果：①斑点杂交表明ｃ－Ｈａ－ｒａｓｍＲＮＡ在进行期斑块型银屑病皮损中含量较正常皮肤增加１倍；②ｃ－Ｈａ－ｒａｓ癌基因在正常皮肤表皮主要表达于部分基底层细胞，而在进行期银屑病皮损内则可见于除角质层外其余各层表皮细胞，且以棘层细胞为主。ｃ－Ｈａ－ｒａｓ癌基因在表皮细胞的过度表达及表达部位的改变可能是银屑病表皮过度增生和异常分化的重要机理。     

Altered [125I]epidermal growth factor binding and receptor distribution in psoriasis

Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normal epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that [125I]EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers.     

Ultrastructural localization of calcium in psoriatic and normal human epidermis

With ion capture cytochemistry, we previously demonstrated the distribution of calcium ions in murine epidermis, a pattern consistent with a role for this ion in the regulation of epidermal differentiation. Because of the known proliferation and differentiation defects in psoriasis, we compared the calcium distribution of involved vs uninvolved psoriatic lesions and normal human epidermis. Whereas normal human and uninvolved psoriatic epidermis revealed increased calcium-containing precipitates in the uppermost stratum granulosum, in contrast the basal layer of psoriatic lesions contained less extracellular calcium, a condition that favored enhanced proliferation. Moreover, all psoriatic suprabasal cell layers displayed heavier than normal concentrations of calcium, indicating loss of the normal calcium gradient that programs terminal differentiation. This abnormal profile may account for the differentiation defects (eg, parakeratosis) that occur in psoriasis. Finally, psoriatic lesions displayed retained ionic Ca in intercellular domains of the upper stratum granulosum with absence of normal intercellular bilayers, findings that may underlie the abnormal desquamation and permeability barrier in psoriasis.     

银屑病皮损中γ干扰素的免疫组化分析

采用γ干扰素（ＩＦＮ－ ）单克隆抗体、双层ＡＰＡＡＰ染色法及显微分光光度测定技术对３０例银屑病患者皮损、１５例正常对照皮肤进行ＩＦＮ－ 抗原的测定。结果显示：除表皮基底层及表皮突下部 １～３层基层外，大量的ＩＦＮ－　抗原阳性染色弥漫分布于皮损全层表皮的角肮细胞间隙；正常对照皮肤的表皮中无明确的ＩＦＮ－　阳性反应；银屑病皮损表皮中ＩＦＮ－　的含量①与银屑病的活动性有关，进行期为２４．３８０８．２５０，静止期为１５．９５５　５．３２７（Ｐ＜０．０１）；②与皮损表皮中Ｔ细胞、ＨＬＡ－ＤＲ细胞的数量呈直线正相关（ｒ１＝０，６９４，ｒ２＝０．４３６，Ｐ＜０．０５）。     

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

Summary Psoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1 was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.     

银屑病患者皮损中Toll样受体2及相关因子的检测

目的探讨Toll样受体2(TLR2)、信号途径下游分子NF-κBp65以及可能的效应分子TGF-α在银屑病患者皮损中的表达及其与银屑病严重程度的关系。方法采用EliVision免疫组化法对40例银屑病患者进行期皮损、11例非皮损区及15例正常人皮肤中TLR2,NF-κBp65,TGF-α的表达进行检测,对其在皮损中的表达进行相关性分析,并将结果与PASI评分进行相关性分析。结果与正常人皮肤及银屑病患者非皮损区相比,银屑病患者皮损表皮中TLR2,NF-κBp65,TGF-α的表达明显上调,而非皮损区TLR2的表达也高于正常人皮肤,差异均有统计学意义(P<0.05)。银屑病患者皮损表皮中TLR2,NF-κBp65的表达水平与PASI评分之间存在正相关(P<0.05)。银屑病患者皮损表皮中TLR2与NF-κBp65,TLR2与TGF-α,NF-κBp65与TGF-α表达水平之间均存在正相关(P<0.05)。结论TLR2,NF-κBp65,TGF-α在银屑病中表达异常,可能共同参与了银屑病的发病过程。     

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.     

Toll样受体2和4在银屑病皮损中的表达

目的研究Toll样受体（TLR）2和4在银屑病皮损中的表达，探讨其与银屑病发病的关系。方法选用16例滴状银屑病、13例斑块状银屑病患者及10例正常人皮肤的石蜡切片．用免疫组化的方法研究TLR2和TLR4的表达。结果10例正常人皮肤的基底层均有较弱的TLR2表达而无TLR4表达．真皮血管内皮细胞未见TLR2及TLR4表达。所有16例滴状银屑病、13例斑块状银屑病皮损的基底细胞层均可见明显的TLR2表达，棘层也有弱表达；TLR4则呈现表皮全层的弥漫性强表达。银屑病真皮浅层血管内皮细胞可见明显的TLR2及TLR4表达。结论TLR2、TLR4在银屑病皮损均有表达，TLR4的表达更高：提示感染相关免疫与银屑病发病关系密切。