Fas Bax和bcl-2蛋白在银屑病病人表皮细胞中的表达

目的观察银屑病病人表皮细胞凋亡中凋亡基因Ｆａｓ、Ｂａｘ（ｂ ｃｅｌ相关基因）和凋亡抑制基因ｂｃｌ ２（Ｂ ｃｅｌＬｙｍｐｈｏｍａ／Ｌｅｕｋｅｍｉａ２）的作用及其相互关系。方法采用免疫组化染色法在３３例银屑病皮损标本中,观察了Ｆａｓ、Ｂａｘ及ｂｃｌ ２蛋白的表达。结果发现３３例银屑病皮损标本中,Ｆａｓ２９例阳性表达;Ｂａｘ２３例阳生;３３例ｂｃｌ ２表达皆阴性。５例正常对照中,Ｆａｓ及Ｂａｘ皆阴性,ｂｃｌ ２在基底层细胞中阳性。结论结果提示Ｆａｓ和Ｂａｘ蛋白的高表达、ｂｃｌ ２的不表达与银屑病损害中表皮细胞凋亡增多有关。     

c－myc、p53和bcl－2与银屑病角质形成细胞凋亡异常关系的研究

目的 探讨原癌基因ｃ－ｍｙｃ、抑癌基因ｐ５３和凋亡保护基因ｂｃｌ－２在银屑病角质形成细胞凋亡异常中的作用。方法 采用免疫组化和非同位素核酸原位杂交技术从蛋白和ｍＲＮＡ二个水平检测了３６份建党型银屑病皮损中ｃ－ｍｙｃ、ｐ５３和ｂｃｌ－２的表达状况。结果 银屑病表皮中的ｃ－ｍｙｃ、ｐ５３和增殖细胞核抗原（ＰＣＮＡ）阳性细胞较正常皮肤明显增加,而ｂｃｌ－２阳性细胞在表皮基底层中明显减少。在ＰＣＮＡ阳性细     

银屑病中细胞凋亡相关基因bcl-2、Fas、bax的检测

为了细胞凋亡相关基因ｂｃｌ－２、Ｆａｓ、ｂａｘ在银屑病发病中的意义,采用免疫组化ＡＢＣ法、ＳＡＢＣ法检测了这几种基因在１５例银屑病中的表达。结果发现银屑病的角质形成细胞中抑凋亡基因ｂｃｌ－２几乎不表达,促凋亡基因Ｆａｓ、ｂａｘ阳性表达。揭示促凋亡基因Ｆａｓ、ｂａｘ在银屑病中发病起重要作用,而抑凋亡基因ｂｃｌ－２作用可能不大。     

光线性角化病皮损细胞Bcl—2基因表达产物的定量分析

Ｂｃｌ－２蛋白是Ｂｃｌ－２基因的表达产物，可抑制细胞凋亡，在某些恶性肿瘤细胞出现过度表达。为探讨Ｂｃｌ－２蛋白与光线性角化病（ＡＫ）的关系，作者用流式细胞免疫荧光技术，检测了２７例ＡＫ。结果显示：２７例ＡＫ及正常对照的Ｂｃｌ－２蛋白相对含量ＦＩ（ＦｌｕｏｒｅｓｃｅｎｃｅＩｎｄｅｘ）分别为１．１５０±０．１８８和０．９９６±０．０６５（Ｘ－±Ｓ），０．０５＜Ｐ＜０．０１。但其中８例不典型增生严重ＡＫ的ＦＩ为１．３３５±０．０１７６（Ｘ－±Ｓ），与正常对照相比Ｐ＜０．０２。提示该病的Ｂｃｌ－２蛋白有增高的倾向。     

银屑病患者皮损中细胞凋亡情况的评价

目的 探讨细胞恨与银屑病的关系。方法 用免疫组化ＳＰ法检测银屑病皮损与非皮损中Ｂａｘ、Ｆａｓ、Ｆａｓ－１的表达,并用ＴＵＮＥＬ（末端脱氧核苷酰转移介导的ｄ－ＵＴＰ－生物素缺口本端标记）技术检测细胞凋亡情况。结果 与正常人相比,银屑病表皮角质形成细胞,真皮炎症细胞及炎症细胞及血管内皮均存在不同程度的上述蛋白的过度表达,伴细胞凋亡增多,部分在治疗后末完全恢复正常。结论 推测银屑病皮损中角质形成对细胞过     

寻常性银屑病皮损中bcl—2 Fas及FasL的表达

目的 探讨银屑病表皮角质形成细胞异常增殖和分化机制。方法 采用免疫组化技术对１０例建党性银屑病皮损中ｂｃｌ－２、Ｆａｓ及ＦａｓＬ表达进行了检测。结果 在建党惺 银屑病皮损中,７例表达ｂｃｌ－２,且表达部位主要位于棘细胞层上方和角质层内角化不全细胞;１０例表达Ｆａｓ,表达部位与ｂａｌ－２相似‘浸润炎性细胞均不表达ＦａｓＬ。相关分析表明,角质形成细胞ｂｃｌ－２和Ｆａｓ表达强度呈显著性相关（ｒ＝－０．７     

银屑病皮损中原癌基因bcl—X的表达及意义

ｂｃｌ－Ｘ是近年来发现的ｂｌｃ－２基因家族的新成员，是一种原癌基因。它具有和ｂｃｌ－２相似的抗凋亡作用。研究发现银屑病皮损中ｂｃｌ－２的表达与正常相似，而ｂｃｌ－Ｘ却有高表达，提示ｂｃｌ－Ｘ与银屑病发病具有相关性。介绍了国外有这方面的研究。提示ｂｃｌ－Ｘ与银屑病的关系对攻克银屑病这一顽病可能具有重要意义。     

皮肤鳞状细胞癌细胞凋亡和Bcl—2,Bax基因的表达

用特异性ＤＮＡ片断标记法（ＴＵＮＥＬ）研究了２５例皮肤鳞状细胞癌（ＳＣＣ）,同时观察了Ｂａｘ和Ｂｃｌ－２基因的表达。结果１９例发现凋亡细胞,６例Ｂｃｌ－２弱阳性以,全部病例Ｂａｘ染色阳性,凋亡均数与Ｂａｘ强度显著正相关,推测ＳＣＣ发生的原因不同由于细胞凋亡受到抑制。     

抗凋亡基因Bcl－2在皮肤角朊细胞肿瘤中的表达

Ｂｃｌ－２是一种原癌基因，它可阻断程序化细胞死亡（细胞凋亡），我们用免疫组化标记Ｂｃｌ－２在１２例基底细胞癌和１０例鳞状细胞癌，结果示正常皮肤基底层细胞呈阳性，基底层以上各层细胞阴性；所有基底细胞癌均呈阳性。提示Ｂｃｌ－２在基底细胞癌的发生、发展中可能起着重要作用。     

Fas、Bcl-2、Ki-67在尖锐湿疣皮损中的表达

目的；探讨尖锐湿疣（ＣＡ）细胞Ｆａｓ，Ｂｃｌ－２，Ｋｉ－６７表达的意义。方法：对２８例ＣＡ用免疫组化法，观察Ｆａｓ，Ｂｃｌ－２及Ｋｉ－６７的阳性表达。     

Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis

BACKGROUND: Infiltration of the skin by pathogenic T cells is regarded as a key factor in the development of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. OBJECTIVES: To investigate whether T cells containing cytotoxic proteins may contribute to the generation of skin inflammation in these skin diseases. METHODS: Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD (n = 8) and psoriasis (n = 6), and from non-atopic controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by immunohistochemistry. RESULTS: A significant enhancement of perforin and granzyme B expression was observed in lesional AD skin as compared with normal skin, non-lesional AD skin and psoriasis. Expression of these cytotoxic proteins was also increased in psoriasis as compared with normal skin and non-lesional psoriatic skin. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells located in the perivascular infiltrate. In AD increased numbers of positive cells were also observed focally at sites of spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. CONCLUSIONS: Our data suggest that cytotoxic CD4+ and CD8+ T cells containing perforin and granzyme B may play an integral part in eliciting cutaneous inflammation in AD.     

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris

Background

A difference of the interleukin-18 (IL-18) mRNA expression among several proinflammatory genes was previously observed between large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and small plaque (SP) psoriasis patients (1~2 cm lesions are typical). Therefore, it is necessary to test whether there is any difference in the expression of the genes that activate IL-18 or the expression of genes that are induced by IL-18.

Objective

To test the differential mRNA expressions of caspase-1, STAT-6, MMP-1, MMP-2, MMP-9 and TIMP-1 according to the clinical types of psoriasis vulgaris lesions in Korean patients, we have analyzed the skin samples of psoriasis vulgaris patients.

Methods

The total cellular RNA of skin samples from groups of patient with LP and SP psoriasis was analyzed by performing real-time PCR (the Taqman method) to compare the differences in the mRNA expressions.

Results

The caspase-1 and STAT-6 mRNA expression levels from the SP lesional skin of the patients were increased compared with the caspase-1 and STAT-6 mRNA expression levels from SP non-lesional skin or normal skin, but these expression levels from the SP non-lesional skin were not significantly different from those of the LP non-lesional skin. Among MMP-1, MMP-2, MMP-9 and TIMP-1, the expressions of MMP-1, MMP-2 and MMP-9 mRNA were increased in the SP lesional skin compared with those of the SP non-lesional skin. The MMP-1 mRNA expressions in both the LP and SP lesional skin were increased compared with those in the normal skin (p=0.028 and p=0.007 respectively). The MMP-9 mRNA expression in the LP non-lesional skin was elevated compared with the MMP-9 mRNA expression in the SP non-lesional skin (p=0.047). The TIMP-1 mRNA expression levels from the non-lesional skin and the lesional skin of the psoriasis patients and the normal skin samples were not significantly different.

Conclusion

The increased expression of MMP-9 mRNA in the LP non-lesional skin compared to that of the SP non-lesional skin in the psoriatic skin suggests that the increased MMP-9 mRNA expression is related to the large size type of lesion.     

银屑病患者角质形成细胞VEGF表达的研究

目的　研究银屑病发病与血管内皮生长因子 (VEGF)的关系 ,探讨银屑病可能的发病机制。方法　①用免疫组化法检测银屑病患者皮损和非皮损处皮肤、正常健康人皮肤及体外培养的银屑病患者和正常人角质形成细胞(KC)VEGF的表达 ;②用双抗体夹心ELISA法检测银屑病患者及正常人KC培养上清液中VEGF含量。结果　①银屑病皮损处VEGF表达明显高于非皮损处和正常人皮肤 (P均 <0 .0 0 1) ,非皮损处与正常人皮肤VEGF表达也有显著性差异 (P <0 .0 5 ) ;②体外培养的银屑病皮损处和非皮损处KCVEGF表达明显高于正常人 (P均 <0 .0 0 1) ;银屑病皮损处KC与非皮损处KC相比VEGF表达也有显著性差异 (P <0 .0 5 ) )。结论　VEGF可能参与银屑病的发病。     

Increased expression of adhesion receptors in both lesional and non-lesional psoriatic skin

Adhesion receptors and their ligands play a vital role in the immune system. We studied the expression of different adhesion receptors, using single- and double-staining immunohistochemical techniques, in both lesional and non-lesional skin specimens from seven psoriasis patients and in skin biopsy specimens from eight normal healthy controls. Our results showed an overall increased expression of several adhesion receptors in both lesional and non-lesional psoriatic skin. We consistently found an increased expression in particular of ICAM-1 and E-selectin on endothelial cells, and ICAM-1 on T cells and Langerhans cells. In contrast, a weak expression of VCAM-1 was found on endothelial cells and mononuclear cells in lesional psoriatic skin specimens alone. Interestingly, LFA-1 was also expressed on Langerhans cells, with a greater frequency in skin from lesional than from non-lesional sites, but was never expressed in skin from normal healthy individuals. Furthermore, significantly increased numbers of Langerhans cells and T cells with a positive reactivity for MAb HECA-452 were found in both lesional and non-lesional psoriatic skin. We hypothesize that the enhanced expression of adhesion receptors on migrating immunocompetent cells and endothelial cells of psoriatic skin in general facilitates the increased influx of activated T lymphocytes and other immunocomponent cells into the skin, and thus underscores the generalized character of the disease.     

Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis.

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.     

寻常型银屑病患者血管内皮生长因子及单核细胞趋化因子-1表达的研究

目的 探讨血管内皮生长因子(VEGF)、单核细胞趋化因子-1(MCP-1)在银屑病患者皮肤中的表达及其意义。方法 用免疫组化法检测银屑病患者皮损、非皮损及正常人皮肤中VEGF、MCP-1的表达与分布。用双抗体夹心酶联免疫吸附法检测患者血清中VEGF、MCP-1水平。结果 ①银屑病患者皮损及非皮损中VEGF表达较正常人皮肤明显增强(P<0.05).皮损中MCP-1表达较非皮损及正常人皮肤明显增强(P<0.05).②患者血清中VEGF水平明显高于正常人(P<0.05),MCP-1水平与正常人比较差异无显着性(P>0.05).③皮损角质形成细胞中VEGF、MCP-1的表达与PASI评分无显着相关性(P>0.05)。结论 VEGF、MCP-1的表达增强在银屑病的发病机制中可能起重要作用。     

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.     

Increased expression of TRAIL and its death receptors DR4 and DR5 in plaque psoriasis

TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (n = 10) and non-lesional (n = 10) skin of patients with plaque psoriasis and skin of healthy volunteers (n = 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.