银杏石榴煎治疗银屑病疗效观察及患者血清中肿瘤坏死因子-α、白介素-6及白介素-8表达水平的变化

目的采用中药银杏石榴煎治疗进行期寻常性银屑病，观察该煎剂对银屑病疗效并检测治疗前后患者血清中肿瘤坏死因子（TNF）-α、白介素（IL）-6及IL-8表达水平变化。方法银杏石榴煎治疗前后对银屑病患者皮损进行PASI评分，采用ELISA法检测银屑病患者治疗前后和正常对照者血清中TNF—α、IL-6及IL-8的表达水平变化。结果①银杏石榴煎可显著改善银屑病患者临床症状，治疗前后PASI评分明显下降（P〈0．01）。②患者血清中TNF-α、IL-6及IL-8水平明显高于正常对照（P〈0．01），治疗后其表达水平较治疗前明显下降（P〈0．05）。③患者体内TNF-α及IL-8表达水平与PASI积分呈正相关（P〈0．05）。结论银杏石榴煎为治疗银屑病的有效药物；患者血清TNF—α、IL-6、IL-8表达水平与银屑病患者的病情变化密切相关。     

甲氨蝶呤对银屑病患者皮损内IL-18的影响

为测定甲氨蝶呤(MTX)对银屑病皮损内白细胞介素18(IL-18)表达的影响.选择15例寻常型银屑病患者和17名正常对照者.利用荧光定量聚合酶链反应法测定正常对照和患者治疗前及治疗6周后皮损内IL-18 mRNA的定量表达.银屑病皮损内IL-18 mRNA的表达水平明显高于正常对照者(P<0.0001).银屑病患者MTX治疗6周后,皮损明显改善,皮损内IL-18 mRNA的表达水平明显低于治疗前的表达水平(P<0.0001).MTX能抑制皮损内IL-18 mRNA的过度表达,恢复Th1型细胞因子平衡,这可能是MTX治疗银屑病的作用机制之一.     

窄谱中波紫外线对寻常型银屑病神经生长因子及其受体mRNA的影响

目的：观察窄谱中波紫外线（NB—UVB）治疗寻常型银屑病的疗效及治疗前后皮损中神经生长因子（NGF）及受体的表达。方法：用NB—UVB治疗23例寻常型银屑病患者,每周3次,连续21次,以PASI评价疗效,并以原位杂交技术和图像分析系统分析皮损部位光疗前后NGF及受体mRNA的表达情况。结果：临床总有效率为91％,光疗后PASI评分较光疗前显著降低（P〈0．001）;光疗前银屑病皮损处NGFmRNA在从基底层到颗粒层均有阳性表达,P140TrkAmRNA在表皮各层均有染色,以棘细胞层和颗粒层染色较强,P75mRNA在棘细胞层和颗粒层有较强染色;光疗后三者mRNA表达强度明显降低（P〈0．01）。结论：NB—UVB是治疗银屑病的安全有效的方法,下调皮损中NGF及受体的表达可能是NB—UVB治疗寻常型银屑病的机制之一。     

甲氨蝶呤对银屑病信号转导和转录激活因子4的表达调控

目的探讨甲氨蝶呤(MTX)对银屑病患者皮损内信号转导和转录激活因子4(STAT4)表达的影响。方法利用荧光定量聚合酶链反应法测定20例寻常性银屑病患者治疗前后皮损内及17例正常对照者皮肤中STAT4mRNA的定量表达,采用直线相关回归方法分析STAT4mRNA的表达与银屑病病情严重指数(PASI)的关系。结果银屑病皮损内STAT4mRNA高于正常对照者的表达水平(P=0.0016)。银屑病皮损内STAT4 mRNA的表达与患者病情严重程度呈显著正相关(P<0.0001)。银屑病患者经过MTX治疗6周后,皮损明显改善,皮损内STAT4 mRNA的表达水平低于治疗前(P=0.0036),与正常对照者的差异无显著性(P=0.0522)。结论STAT4可能在银屑病的发病中起重要作用。MTX能抑制银屑病皮损内STAT4 mRNA的过度表达,这可能是MTX治疗银屑病的作用机制之一。     

银屑病皮损VDR表达水平的研究

为了解维生素D受体（VDR）在银屑病皮损中的表达情况,采用RT－PCR方法检测了10例寻求型银屑病患者皮损VDR mRNA表达水平,并与正常人皮肤做对照。结果显示：寻常型银屑病患者皮损VDR mRNA水平明显低于 正常人皮肤（P＜0．05）,寻常型银屑病皮损VDR mRNA水平下降,可能与银屑病的发病有一定的关系。     

寻常性银屑病患者外周血及皮损中miR-155的表达及其与Th17细胞的相关性

目的检测寻常性银屑病患者外周血与皮损组织中miR-155,Th17细胞特异性转录因子RORγt及效应性细胞因子IL-17的表达情况并探讨其相关性。方法实时荧光定量RT-PCR检测42例寻常性银屑病患者外周血单一核细胞(PBMCs)及8例皮损组织中miR-155表达情况及RORγt,IL-17的mRNA表达情况,酶联免疫吸附试验(ELISA)检测患者血清IL-17水平。并以同期35例性别和年龄匹配的健康体检者外周血及5例正常皮肤组织标本作为对照。结果寻常性银屑病患者PBMCs中miR-155表达,RORγt与IL-17的mRNA表达及血清IL-17水平均明显高于健康对照者(P均0.01),miR-155表达与RORγt和IL-17的mRNA表达、IL-17血清水平及皮损面积与疾病严重程度评分(PASI)呈正相关(P均0.01);寻常性银屑病患者皮损、皮损周围组织及正常皮肤组织间miR-155,RORγt和IL-17 mRNA的表达差异均有统计学意义(皮损皮损周围组织正常皮肤组织,P均0.01),皮损及皮损周围组织中miR-155表达与RORγt,IL-17的mRNA表达呈正相关(P均0.01)。结论寻常性银屑病患者外周血及皮损组织中miR-155高表达,且与Th17细胞特异性转录因子及效应性细胞因子高表达相关,参与银屑病的疾病过程。     

特应性皮炎患者皮损内IL-8 mRNA的表达及意义

目的：探讨特应性皮炎（AD）患者皮损内白细胞介素8（IL-8）的表达及其临床意义。方法：采用荧光定量聚合酶链反应法测定22例AD患者皮损内及20例正常对照者皮肤内IL-8 mRNA的定量表达,采用湿疹面积及严重度指数（EASI）评分评估患者病情,分析AD患者皮损内IL-8 mRNA的定量表达与EASI评分相关性。结果：AD患者皮损内IL-8 mRNA的表达明显高于对照组皮肤内的表达（t=22.96,P〈0.01）;AD患者皮损内IL-8 mRNA的定量表达与EASI评分呈正相关（r=0.71,P〈0.01）。结论：AD皮损内IL-8 mRNA的过度表达可能与AD的发病有关。     

凉血活血复方治疗寻常型银屑病及对血清IL-8的影响

应用凉血活血复方治疗寻常型银屑病患者，采用PASI评分判定疗效，ELISA法检测治疗前后血清IL-8水平。结果：患者疗后PASI评分及血清IL-8水平均较疗前显著降低（P〈0．001），其血清IL-8水平与其相应PASI评分问呈线性正相关（r=0．624，P〈0．01）。凉血活血复方治疗寻常型银屑病临床疗效满意，其机制可能与下调IL-8的水平有关，血清IL-8水平的检测可作为判定疗效的一项指标。     

消银合剂治疗血热证银屑病疗效及血清干扰素-γ、白介素-10检测

目的观察消银合剂对寻常性银屑病进行期血热证的临床疗效，并探讨其对银屑病Th1／Th2漂移的影响。方法选择寻常性银屑病进行期血热证患者60例，随机分为治疗组30例和对照组30例。治疗组给予消银合剂，对照组给予复方青黛胶囊，疗程8周。观察治疗前后PASI评分的变化，并测定30例治疗组患者治疗前后及20例正常对照者血清干扰素（INF）-γ、白介素（IL）-10水平。结果①治疗8周后，两组PASI积分均明显下降，治疗组PASI积分明显低于对照组（P〈0．05）。②治疗组有效率96．66％，优于对照组86．67％（P〈0．05）。③与正常对照相比，患者组INF-γ水平及INF-γ／IL-10比值明显升高，IL-10水平明显降低（P〈0．001）。治疗前PASI评分与血清INF-γ、IL-10水平均呈正相关（r=0．7，P〈0．001；r=0．43，P〈0．02）。治疗8周后，患者组血清INF-γ、IL-10水平，INF-γ/IL-10与健康对照组相比，无明显差异（P〉0．05）。结论消银合剂可能通过调节患者异常的INF-γ、IL-10水平而治疗银屑病。     

Sharpin蛋白在寻常型银屑病皮损内的表达及其与PASI评分关系的研究

目的:探讨Sharpin蛋白在寻常型银屑病皮损内的表达及其与PASI评分的关系。方法:采用实时荧光定量PCR及免疫组织化学方法检测Sharpin在寻常型银屑病及正常皮肤内的表达,并探讨其与临床病理特征的关系。结果:Sharpin mRNA在寻常型银屑病皮损内较正常皮肤内表达明显升高,两者差异有统计学意义(t=0.03,P0.05);免疫组化结果提示Sharpin蛋白在寻常型银屑病皮损内高表达,且在寻常型银屑病皮损内的阳性表达率高于正常皮肤组织,平均染色得分亦高于正常皮肤(P值均0.05)。此外,Sharpin蛋白表达与治疗前寻常型银屑病PASI评分呈正相关(r=0.83,P0.05)。结论:Sharpin蛋白可能参与了银屑病发病机制,对提示银屑病病情及预后可能具有一定的意义。     

银屑病皮损中IL—1受体拮抗物的蛋白和mRNA表达

采用抗人ＩＬ－１ｒａ单抗和地高辛标记的ＲＮＡ探针,在银屑病破损和正常人皮肤切片上进行ＡＰＡＡＰ染色和原位杂交,检测并比较ＩＬ－Ｉｒａ的蛋白表达和ｍＲＮＡ转录水平。结果发现,正常人皮肤中ＩＬ－１ｒａ蛋白染色阴性,ＩＬ－１ｒａｍＲＮＡｗ信号微弱;相比之下,银屑病皮损中ＩＬ－１ｒａ蛋白和ｍＲＮＡ的表达均异常增高,统计学比较相差显著。上述结果显示：ＩＬ－１ｒａ在银屑病皮损中增强表达,提示银屑病病理过程中Ｉ     

Mast cell density and IL-8 expression in nonlesional and lesional psoriatic skin

BACKGROUND: An important cellular aberration at sites of psoriatic inflammation is an increase in the number of dermal mast cells. Being multifactorial immune effector cells, it is believed that mast cells play an essential role in perpetuating the inflammatory process of psoriasis. However, factors responsible for the infiltration and accumulation of mast cells in psoriatic lesions are largely unknown. Recent studies have demonstrated that Interleukin-8 (IL-8) exerts strong chemotactic effects on mast cells in vitro. Overexpression of IL-8 has also been reported in psoriatic lesions. In this study, we have found a correlation between the expression of IL-8 and dermal mast cell density in lesional psoriatic skin as compared to nonlesional psoriatic skin. METHODS: Four-mm punch biopsies were taken from 14 psoriatic patients and eight healthy volunteers. Using immunohistochemical techniques, 8 microm sections of lesional psoriatic, nonlesional psoriatic, and normal control samples were evaluated for dermal mast cell density and the density of IL-8 expressing keratinocytes. RESULTS: It was found that dermal mast cell density in lesional psoriatic, nonlesional psoriatic, and normal skin was 105.4 +/- 71.2, 42.3 +/- 30.1, and 47.5 +/- 32.5 mast cells/mm(2), respectively. IL-8+ keratinocyte density in lesional psoriatic, non lesional psoriatic, and normal skin was 171.5 +/- 67.1, 25.4 +/- 14.9 and 20.6 +/- 8.7 IL-8+ Keratinocytes/mm(2), respectively. CONCLUSIONS: The results of this study suggest that increased levels of IL-8 in the keratinocytes of psoriatic plaques play a contributing role in the migration of mast cells to lesion sites.     

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。     

Expression of IL-18 in psoriasis

Abstract Interleukin-18 (IL-18) is a novel cytokine that plays an important role in the T-helper 1 (Th1) response, primarily via its ability to induce IFN-γ production in T cells and NK cells. Human keratinocytes produce IL-18, as do monocytes and macrophages, which are the two major sources of this molecule. It is thought that IL-18 derived from keratinocytes might be involved in the cutaneous Th1-type immune response. In the present study, we investigated the expression of IL-18 in psoriatic lesional skin and attempted to determine whether immunoreactive IL-18 in crude extracts of psoriatic scales is processed to the mature, active form. Immunohistochemical and RT-PCR analysis showed that the expression of IL-18 was increased in psoriatic lesional skin relative to that in normal skin. Western blotting and an ELISA for IL-18 in combination demonstrated that the immunoreactive IL-18 in extracts of psoriatic scales contained the mature form of IL-18, but most of the IL-18 was pro-IL-18. No bioactivity of IL-18 or IFN-γ inducibility in human PBMC could be detected in psoriatic scales. Taken together, these findings indicate that keratinocyte-derived IL-18 participates in the development of the Th1 response in psoriatic lesions, and that its bioactivity appears to be tightly regulated in cutaneous inflammation. Received: 18 October 2000 / Revised: 3 February 2001 / Accepted: 27 April 2001     

The activity of caspase-1 is increased in lesional psoriatic epidermis

Caspase-1 belongs to the group of inflammatory caspases and is the activating enzyme for the proinflammatory cytokine IL-18, a cytokine known to play an important role in the pathogenesis of psoriasis. The purpose of this study was to determine the expression of caspase-1 in psoriatic skin and the signaling mechanisms involved in stress-induced activation of caspase-1 and IL-18. Interestingly, increased caspase-1 activity in lesional compared with non-lesional psoriatic skin was seen. In vitro experiments in cultured human keratinocytes demonstrated anisomycin-induced, p38 mitogen-activated protein kinase (p38 MAPK)-dependent increased secretion of procaspase-1 and active caspase-1. Furthermore, anisomycin increased the mRNA expression of IL-18 through a p38 MAPK-dependent but caspase-1-independent mechanism, reaching a maximum level after 12 hours of stimulation. Finally, anisomycin caused a rapid (4 hours) increase in the secretion of proIL-18 and active IL-18. Secretion of active IL-18 was mediated through a p38 MAPK/caspase-1-dependent mechanism, whereas secretion of proIL-18 was mediated by a p38 MAPK-dependent but caspase-1-independent mechanism. These data demonstrate that the activity of caspase-1 is increased in psoriatic skin and that IL-18 secretion is regulated by a p38 MAPK/caspase-1-dependent mechanism, making caspase-1 a potential target in the treatment of psoriasis.