寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

寻常性银屑病患者外周血单核细胞自然状态下合成和分泌的TNF-α生物学活性研究

TNF-α分为分泌型TNF-α(sTNF-α)和膜相关型TNF-α(MA-TNF-α).sTNF-α可通过其相应受体结合在单一核细胞膜上,形成膜结合型TNF-α,简称膜TNF-α.TNF-α是银屑病免疫炎症反应的重要介质,在银屑病的病理过程中发挥重要作用[1].     

Disseminated granuloma annulare: a cutaneous adverse effect of anti-tnf agents

Tumor necrosis factor-alpha (TNF-α) inhibitors, such as etanercept, infliximab, and adalimumab, bind to TNF-α and thereby act as anti-inflammatory agents. This group of drugs has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, moderate to severe plaque psoriasis, ankylosing spodylitis, Crohn disease, and juvenile idiopathic arthritis. We describe a 56-year-old woman who developed an erythematous pruritic rash on both arms-diagnosed as granuloma annulare by skin biopsy-approximately 22 months after initiating adalimumab for treatment of rheumatoid arthritis. On stopping adalimumab there was total clearance of the skin lesions, but a similar rash developed again when her treatment was switched to another anti-TNF agent (etanercept). This clinical observation supports a link between TNF inhibition and the development of granuloma annulare.     

肿瘤坏死因子α抑制剂在皮肤科的应用

肿瘤坏死因子α是由多种细胞分泌的一种炎性因子,其抑制剂目前市场上有3种:英利昔单抗、依那西普及阿达木单抗.在皮肤科领域,美国食品药物管理局仅批准本类药物用于银屑病及银屑病性关节炎的治疗.但近年来越来越多的研究证实,TNF-α抑制剂可用于更多类型皮肤疾病的治疗,并成功治疗了如化脓性汗腺炎、坏疽性脓皮病和毛发红糠疹等多种其他类型的炎症性皮肤病.为此,概述肿瘤坏死因子α抑制剂在治疗皮肤疾病中的应用进展.     

肿瘤坏死因子α对角质形成细胞产生白介素8和增殖活性的影响

目的 了解肿瘤坏死因子α(TNF-α)、肿瘤坏死因子受体Ⅰ(TNFRⅠ)和抗TNFRⅠ抗体对银屑病患者角质形成细胞(KC)产生白介素8(IL-8)和增殖活性的影响.方法 分离表皮细胞接种96孔板,分别为:①自然增殖孔;②TNF-α刺激孔;③sTNFRⅠ/TNFα培养孔;④sTNFRⅠ/抗TNFRⅠ/TNF-α培养孔;⑤抗TNFRⅠ/TNF-α培养孔.ELISA法测上清液IL-8的含量;MTT法测增殖活性;收集细胞提取RNA进行反转录和扩增,产物电泳后转膜,进行DNA印迹以比较IL-8的表达在转录水平上的差异.结果 银屑病患者组所测3个指标均较正常对照组高(P<0.05);两组TNF-α刺激孔KC3个指标均显着高于自然增殖孔和sTNFRⅠ/抗TNFRⅠ/TNF-α培养孔;自然增殖孔和sTNFRⅠ/抗TNFRⅠ/TNF-α培养孔之间比较差异无显着性.结论 ①银屑病患者KC处于活化状态,分泌高水平细胞因子且增殖活跃;②TNF-α可诱导体外培养KC表达IL-8mRNA和蛋白,促进KC增殖,其作用可能主要是通过和细胞表面TNFRⅠ结合来实现;③sTNFRⅠ可以部分阻断TNF-α的生物学作用.     

寻常型银屑病患者中性粒细胞分泌炎性因子的研究

目的观察寻常型银屑病患者外周血中性粒细胞是否存在分泌炎性因子的异常,探讨中性粒细胞参与银屑病的机制。方法作中性粒细胞培养,应用酶联免疫吸附法检测脂多糖(LPS)刺激前后中性粒细胞分泌白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)的水平,应用细胞色素C还原法检测LPS刺激前后中性粒细胞超氧阴离子(Superox-ide anion)的水平。结果在脂多糖刺激前、后,银屑病患者外周血中性粒细胞分泌的IL-8、TNF-α以及Superoxide anion水平均较正常人显著增高(P<0.05),且进行期患者上述炎性因子的分泌水平显著高于静止期患者(P<0.01)。银屑病患者病情严重程度(PASI评分)与中性粒细胞于脂多糖刺激前、后IL-8、TNF-α及Superoxideanion水平均呈正相关(P<0.05)。结论银屑病患者存在外周血中性粒细胞分泌炎性因子的异常,该种异常可能参与银屑病的发病与病情进展,其中可能有感染因素的介导。     

Interleukin (IL)-17 versus IL-27: opposite effects on tumor necrosis factor-α-mediated chemokine production in human keratinocytes

Tumor necrosis factor (TNF)-α is known to play a pivotal role in the pathogenesis of psoriasis. TNF-α has been shown to act directly on keratinocytes, thereby inducing the production of various kinds of chemokines, which contributes to the infiltration of leucocytes into the psoriatic lesions. Recent studies have shown that both interleukin (IL)-17 and IL-27 are increased in psoriatic lesional tissue. However, the interactions between TNF-α, IL-17 and IL-27 in chemokine production by keratinocytes have not been fully elucidated. Here, we examined in human keratinocytes how TNF-α, IL-17 and IL-27 affect production of chemokines that are involved in the pathogenesis of psoriasis. We found that IL-17 and IL-27 exert opposite effects on TNF-α-mediated chemokine production. This suggests that lesional balance of IL-17 and IL-27 is involved in the recruitment of T cells, natural killer cells, neutrophils, monocytes or dendritic cells, thereby affecting inflammation in skin diseases.     

银屑病患者骨髓基质细胞分泌TNF-α,LIF和HGF的分析

目的通过比较银屑病患者与对照组骨髓基质细胞分泌肿瘤坏死因子-α(TNF-α)、白血病抑制因子(LIF)和肝细胞生长因子(HGF)水平的差异,揭示银屑病患者骨髓造血微环境的异常。方法采用密度梯度离心法分离患者与对照组骨髓单一核细胞,通过贴壁法培养骨髓基质细胞,收集传代3次后又培养72h的骨髓基质细胞及培养上清,用流式细胞仪鉴定细胞表面标志并用ELISA法检测上清液中TNF-α,LIF和HGF的水平。结果90%以上细胞表面抗原高表达CD29,而CD34,CD45及HLA-DR表达阴性,即骨髓基质细胞纯度在90%以上;患者组骨髓基质细胞分泌TNF-α,LIF和HGF均显著低于对照组(P<0.05)。结论银屑病患者骨髓基质细胞分泌的某些细胞因子存在异常,表明患者骨髓造血微环境可能存在异常。     

Normal response to tumor necrosis factor-alpha and transforming growth factor-beta by keratinocytes in psoriasis

Abstract Normal and chronic plaque psoriatic keralinocyte cultures were tested for their in vitro response to 2–200 ng/nil TNF-α and 0.1–10 ng/ml TGF-β in a serum-free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose- and lime-dependent inhibition of growth in response to TNF-α and TGF-β. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF-α and 0.1 ng/ml for TGF-β at day 2, but became significant at 20 ng/ml and 1 ng/ ml for TNF-α and TGF-β respectively at days 2-6. This effect was statistically significant at days 3–4 for the group of normal (TNF-α and TGF-β, n = 10, p<0.01 and psoriatic cultures (TNF-α. n = 9, p<0.0l; TGF-β, n = 7, p<0.05). Epidermal cells from normal and psoriatic skin were inhibited to the same extent at the same optimal concentrations by each cytokine. Inhibition was abolished by the addition of specific antibody to each cytokine, whilst antibody to a different cytokine had no effect. Nuclear and/or nuclear membrane staining was observed with antibody to the p55 TNF receptor both in cultured keralinocyles and in the tipper epidermal layers of both normal and psoriatic skin. In contrast, plasma membrane and cytoplasmic expression of the p55 TNF receptor was observed on macrophages and lymphocytes infiltrating psoriatic der-mis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF-α and TGF-βin vitro. The expression of TNF receptor by psoriatic keratinocytes in vivo may permit regulation of epidermal growth by administration of TNF-α in this disease.     

Interleukin-1 family members are enhanced in psoriasis and suppressed by vitamin D and retinoic acid

Interleukin (IL)-1 family comprise 11 members that play an important role in immune regulation and inflammatory process. Retinoids exert complex effects on the immune system, having anti-inflammatory effects in chronic dermatological diseases. Vitamin D (vitD) and analogs have been shown to suppress TNF-α-induced IL-1α in human keratinocytes (KCs). In the present study, we investigated IL-1 family members in psoriasis and the effects of vitD and retinoic acid (RA) on these members. We analyzed IL-1 family members gene expression in psoriatic skin and in ex vivo skin organ culture exposed to TNF-α, IL-17 or broadband UVB; afterwards, treatment with vitD or RA was performed and IL-1 family members mRNA was evaluated. Similarly, KCs were stimulated with IL-17 and subsequently treated with vitD. IL-1 family members were enhanced in psoriatic skin and in ex vivo skin organ cultures after pro-inflammatory stimuli (TNF-α, IL-17 and UVB). RA and vitD were able to suppress this enhancement.     

Study of genetic polymorphisms in the tumor necrosis factor α promoter region in Spanish patients with psoriasis

BackgroundSeveral studies have reported an association between tumor necrosis factor α (TNF-α) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population.ObjectiveTo analyze the polymorphisms of the promoter region of the TNF-α gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers.Material and methodsEighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-α promoter region of both groups were genotyped.ResultsWe observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant.ConclusionThere are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-α plays in the pathophysiology of this disease.