Lesional elastase activity in psoriasis, contact dermatitis, and atopic dermatitis.

Human leukocyte elastase (HLE) is a broad spectrum serine protease derived from neutrophils and macrophages. We developed an assay to determine HLE activity on the skin surface in patients with inflammatory skin diseases. HLE activity was absent in the skin of healthy controls. A massive increase of HLE activity was found in lesional skin of psoriasis (31 times), allergic contact dermatitis (55 times), and atopic dermatitis (35 times), but not in uninvolved skin of diseased patients. Therefore, this assay appears to represent a useful biochemical marker of epidermal inflammation. The presence of proteolytically active HLE in diseased epidermis, which is known to contain specific inhibitors of this enzyme, suggests a pathophysiologic role of this enzymatic activity in psoriasis, contact dermatitis, and atopic dermatitis.     

Basement membrane zone as a target for human neutrophil elastase in psoriasis

Summary Human neutrophil elastase was found, by indirect immunofluorescence using rabbit anti-elastase antiserum, to be bound to basement membrane of psoriatic plaques in vivo. The enzyme was also identified inside the migrating neutrophils in the reticular dermis and dermal papillae, as well as outside the cells in micro-abscesses in psoriatic skin. In vitro incubation of normal skin with human neutrophil elastase resulted in the destruction of hemidesmosomes and separation of the epidermis from the dermis above localizations of bullous pemphigoid antigen. These findings are direct evidence that human neutrophil elastase could play a role in psoriasis in in vivo destruction of the epidermal — dermal junction.     

银屑病皮损表皮中表皮生长因子的免疫组化研究

用一种新的免疫组化技术标记的抗生蛋白链菌素－生物素连接系统对２４例银屑病患者皮损 及１０例正常人表皮中的表皮生长因子进行了免疫组化研究。结果表皮生长因子阳性染色细胞主要分布 于棘层和颗粒层。银屑病患者表皮生长因子阳性表达率为７５％。表皮生长因子阳性表达率及阳性细胞 密度在静止期与进行期之间及初发病例与复发病例之间均无统计学差异（Ｐ均＞０．０５）。     

Decreased specific anti-elastase activity in the uninvolved skin of patients with psoriasis

Summary Inhibitory activities against elastase, chymotrypsin and trypsin were studied in the fluid from experimentally developed suction blisters in the uninvolved skin of patients with psoriasis. These activities determined by spectrophotometry of specific synthetic low molecular weight substrates were compared with respective antiproteinase activities in sera of 32 patients with psoriatic lesions, ten patients in remission, and ten healthy volunteers. A marked reduction (29.2%) in the specific elastase inhibitory activity of blister fluid was found in patients with psoriasis when compared with normal subjects (p<0.05), since neither chymotrypsin nor trypsin inhibitory activities were altered. This reduction was despite about a 30% increase in the elastase inhibitory activity in the sera of these patients, which was related presumably to their increased activity of ₁-proteinase inhibitor, the main serum antiserine proteinase inhibitor. A decreased blister fluidserum elastase inhibition ratio was shown in a large majority of patients with psoriasis, even in symptomless patients. The deficiency in specific elastase inhibitory activity of suction blister fluid was predominantly associated with early onset of psoriasis, guttate lesions and inactive lesions, skin involvement less than 20% of body surface, duration of relapse shorter than 2 months, and frequent relapses. These data indicate that the uninvolved skin of patients with psoriasis contains low concentrations of specific elastase tissue inhibitor, which deficiency might result in an excessive in vivo hydrolytic activity of neutrophil elastase released from migrating cells in the psoriatic skin.     

Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity

BackgroundIn recent studies, microRNAs (mi-RNAs) have been shown to play an important role in psoriasis pathogenesis. However, studies evaluating mi-RNAs in the blood of psoriasis patients including a large number of mi-RNA panels are scarce.ObjectiveThe authors aimed to assess mi-RNA expressions in blood samples of psoriasis patients, as well as to evaluate the association between mi-RNA expression and psoriasis severity.MethodsThis was a case-control study on 52 patients with psoriasis vulgaris and 54 controls. Patients’ medical history, psoriasis area and severity index (PASI) scores, and dermatology life quality index (DLQI) scores were recorded. The 42 disease-related mi-RNA primers were assessed by real-time PCR.ResultsIn the patient group, 13.4% presented nail involvement and 8.2% had psoriatic arthritis. The mean PASI and DLQI scores were 7.90 ± 8.83 and 8.13 ± 5.50, respectively. Among 42 mi-RNA primers; hsa-miR-155-5p, hsa-miR-369-3p, hsa-miR-193b-3p, hsa-miR-498, hsa-miR-1266-5p, hsa-let-7d-5p, hsa-miR-205-5p, hsa-let-7c-5p, hsa-miR-30b-3p, and hsa-miR-515-3p expressions were significantly up-regulated, whereas hsa-miR-21-5p, hsa-miR-142-3p, hsa-miR-424-5p, hsa-miR-223-3p, hsa-miR-26a-5p, hsa-miR-106b-5p, hsa-miR-126-5p, hsa-miR-181a-5p, hsa-miR-222-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-17-3p, hsa-miR-30b-5p, hsa-miR-130a-3p, hsa-miR-30e-5p, and hsa-miR-16-5p were significantly down-regulated in psoriasis patients when compared with the control group (p < 0.05).Study limitationsAs the study included patients with mild to moderate psoriasis who mostly only received topical treatments, changes in miRNA before and after systemic treatments were not assessed.ConclusionThe detection of 24 mi-RNA expressions up- or down-regulated in psoriasis patients, even in those with milder disease, further supports the role of mi-RNAs in the psoriasis pathogenesis. Future studies should clarify whether mi-RNAs can be used as a marker for psoriasis prognosis or as a therapeutic agent in the treatment of psoriasis.     

银屑病患者血清中可溶性选择素E水平与疾病严重程度分析

应用ELISA法测定寻常型银屑病患者治疗前(31例),治疗后(30例)和正常人(20名)血清中可溶性选择素E水平。结果显示治疗前银屑病患者血清中可溶性选择素E水平显著高于正常人(t=3.277,P<0.005),并且与疾病严重程度(PASI记分)呈正相关(r="0.495,P<"0.005)。治疗后随病情好转,可溶性选择素E水平显著下降(t="3.119,P<"0.005),此下降现象在原PASI相对较高的患者中表现得更为明显。本文结果表明,血清中可溶性选择素E水平与寻常型银屑病患者病情相关,可作为判定银屑病活动性的一个有用指标。     

银屑病基因-环境、基因-基因交互作用研究进展

目前认为银屑病主要由环境因素和遗传因素等共同作用所致。环境因素如吸烟、饮酒、外伤等可诱发或加重银屑病病情［１］。遗传学研究发现,PSORS1-9、HLA-Cw*0602、IL12B、IL23R、ERAP1等位点或基因与银屑病的易感性相关联［2］。近年来,研究者利用多种方法开展银屑病基因-环境、基因-基因交互作用方面的研究,阐明其在银屑病发病机制中的作用,取得了进展……     

Studies on the role of polymorphonuclear leukocyte granule elastase in arthus reaction

Summary In the present study, attempts were made to clarify the role of an elastase-like enzyme in Arthus reaction by using rabbit-peritoneal polymorphonuclear leukocytes (PMNs). It was first confirmed that the injection of large amounts of PMNs with antibody can increase tissue damage in reversed Arthus reaction. The five various fractions, which were intact PMNs, whole homogenate, granule fraction, nuclei and cell debris, and membrane extract, were prepared from rabbit-peritoneal exudate. Each fraction was intracutaneously injected into the abdominal wall of rabbit. It was of particular interest that the tissue damage induced by membrane extract occurred earlier and was more severe than that caused by the others. Furthermore, membrane extract possessed remarkably higher caseinolytic and elastinolytic activities than the others. The membrane extract was partially purified by Sephadex G-100 column chromatography. The protein concentration of the elastase-like enzyme solution was 3.64 mg/ml, and its specific activity was 195 caseinolytic units and 0.45 elastinolytic units per milligram of protein. The cutaneous reaction by membrane extract was dependent on the concentration of this elastase-like enzyme and could be strongly inhibited by Elastatinal. From these results, the authors suggest that an elastase-like enzyme which originates in PMN granules is the key enzyme that promotes the severity of tissue damage in Arthus reaction.     

结合珠蛋白在银屑病皮损及皮损周边外观正常皮肤中的表达

目的 从mRNA及蛋白质水平研究结合珠蛋白在银屑病皮损及皮损周边外观正常皮肤中的表达,探讨其与朗格汉斯细胞的关系及在银屑病发病中的作用.方法采用免疫组化、免疫荧光双标记和原位杂交技术检测银屑病皮损及皮损周边外观正常皮肤中结合珠蛋白的表达.结果与正常人皮肤相比,银屑病皮损处角质形成细胞中结合珠蛋白mRNA的表达均明显增强(P＜0.001);皮损周边外观正常皮肤中的表达与正常人皮肤差异无显著性(P＞0.05).免疫组化显示:皮损处部分角质形成细胞胞浆中有结合珠蛋白表达;皮损及皮损周边外观正常皮肤中均可见结合珠蛋白在部分朗格汉斯细胞中呈阳性表达,且两者中结合珠蛋白阳性朗格汉斯细胞与朗格汉斯细胞总计数的比值较正常皮肤显著增高(P＜0.001).结论银屑病皮损处角质形成细胞中结合珠蛋白mRNA的表达增强,并能合成结合珠蛋白.合成结合珠蛋白的角质形成细胞可能在银屑病发病机理中起负反馈调节作用。     

头皮银屑病

头皮银屑病因为其影响美观和治疗困难而受到患者的重视。随着现代医学的发展,银屑病的病因学、治疗学研究都取得了很大的进步,针对头皮银屑病的治疗也有了新进展。许多国家和地区相继出台了头皮银屑病的治疗指南和意见［1-3］。2013年中华医学会皮肤性病学分会银屑病学组制定了2013版中国银屑病治疗指南［4］,对头皮银屑病的治疗模式进行了阐述。本文综述了目前国际上头皮银屑病的研究现状……     

A study on the candida-killing activity of polymorphonuclear leukocytes in patients with psoriasis vulgaris

Summary The Candida albicans killing capacity, a function of polymorphonuclear leukocytes from patients with psoriasis vulgaris was significantly higher than that of granulocytes from healthy persons. This observation is a further data supporting the concept of the activated granulocyte in psoriasis.     

Generalized pustular psoriasis (von Zumbusch)

Generalized pustular psoriasis (von Zumbusch) is a rare and acute eruption characterized by multiple sterile pustules over an erythematous and edematous background, eventually associated with psoriasis vulgaris. Classically, it manifests as a potentially severe systemic picture and demands prompt diagnosis and intervention. The duration of each flare-up and intervals between the pustular episodes is extremely variable. Recently, genetic abnormalities have been identified mainly in the familial and early variants of this disease. The therapeutic arsenal is limited; however, new drugs being evaluated aim to control both pustular flare-ups and disease recurrences.     

microRNA与银屑病

miemRNA是近年来发现的一组非编码单链小分子RNA,其对基因表达进行转录后调控,在许多疾病中都有异常表达,是疾病发生的总"开关".与正常皮肤组织和其他炎症性皮肤病(如特应性皮炎)比较,银屑病皮损有特异性microRNA表达异常.研究这些特异性microRNA在银屑病中的作用,对银屑病发病机制的阐明具有一定意义.     

Growth hormone levels in psoriasis

Summary Plasma growth-hormone levels in 12 fasting psoriatics were 4.4±1.4 mU/l (mean±SEM), compared to 2.7±1.7 in 5 patients with eczema and 1.2±0.3 in 6 normal subjects. The differences in mean values were not statistically significant and were due to exceptionally high levels of growth hormone in five patients with psoriasis and one patient with eczema. In the psoriatic group the exceptional patients were not distinguished by age or the area of involved skin but they tended to be leaner than those with low plasma-growth hormone levels. We conclude that raised plasma growth hormone cannot be the cause of psoriasis but might be a secondary effect of the skin disease in some patients.     

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     

Enhanced procoagulant acticity of mononuclear leukocytes in patients with atopic dermatitis and psoriasis

Fibrin deposition is an important histopathological feature of inflammatory skin lesions and is mediated in part, by procoagulants generated by mononuclear leucocytes (MNL). We examined whether MNL from patients with atopic dermatitis or psoriasis generate enhanced procoagulant activity (PCA). MNL isolated from the peripheral blood of 15 healthy control individuals, 15 patients with atopic dermatitis and 15 patients with psoriasis were incubated for 24 h in the presence or absence of bacterial lipopolysaccharide (LPS). MNL or the cell culture supernatants were then added to recalcified human plasma to determine the clotting time. We found that in both atopic dermatitis and psoriasis MNL cultured in the presence or absence of LPS expressed greatly enhanced PCA (p<0.01 to <0.002). Supernatants from MNL cultures from patients with psoriasis, but not those from patients with atopic dermatitis, also generated augmented PCA (p<0.002). In psoriasis, PCA normalized after successful topical treatment with anthralin. We conclude that enhanced PCA is a characteristic feature of MNL in both atopic dermatitis and psoriasis. In psoriasis the enhanced PCA is directly related to disease activity.This paper contains data from the doctoral thesis of H. W.     

人淋巴细胞转移因子对银屑病患者自然杀伤细胞活性的影响

本文用ＬＤＨ释放法测定了应用转移因子前后的银屑病患者外周血ＮＫ细胞活性，结果显示转移因子能显著地提高其ＮＫ细胞的杀伤活性，揭示了转移因子对银屑病患者细胞免疫功能的调节作用，佐证了其临床应用价值。同时讨论了转移因子对银屑病患者ＮＫ细胞的作用机制。     

脂肪因子与银屑病

银屑病发病机制涉及遗传、免疫等多种因素。近年来逐渐认识到银屑病是一种系统性疾病,与肥胖、高血压、糖尿病及代谢综合征等相关。脂肪组织可以通过分泌脂肪因子介导胰岛素抵抗、炎症调控、内皮功能障碍及动脉粥样硬化等异常。脂肪因子如瘦素、抵抗素、chemerin、脂联素及内脂素等在银屑病中表达异常,可能参与银屑病发病机制中的免疫应答及表皮异常增殖。