THE CYTOKINE NETWORK IN LESIONAL AND LESION-FREE PSORIATIC SKIN IS CHARACTERIZED BY A T-HELPER TYPE-1 CELL-MEDIATED RESPONSE

THE CYTOKINE NETWORK IN LESIONAL AND LESION-FREE PSORIATIC SKIN IS CHARACTERIZED BY A T-HELPER TYPE-1 CELL-MEDIATED RESPONSE
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DOI:
10.1111/1523-1747.ep12371679
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发表时间:
1993-11-01
影响因子:
6.5
通讯作者:
NICKOLOFF, BJ
NICKOLOFF, BJ
中科院分区:
医学1区
文献类型:
--
作者:
UYEMURA, K;YAMAMURA, M;NICKOLOFF, BJ

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由于银屑病病变发生在以前未累及的皮肤部位,细胞因子及其随后诱导的各种粘附分子可能发挥重要的病理生理作用。 为了进一步确定银屑病中的细胞因子网络,从银屑病个体的病变皮肤和无病变皮肤获得活检组织,并与对照受试者的正常皮肤活检组织进行比较。使用聚合酶链反应分析每个活检组织的细胞因子表达和免疫染色以检测粘附分子。结果表明银屑病病变具有1型细胞因子谱(即,白细胞介素[IL]-2,干扰素[IFN]-γ,和肿瘤坏死因子[TNF]-α),而没有2型细胞因子的显著组分(即,IL-4、IL-5和IL-10),伴有真皮内皮细胞上内皮细胞白细胞粘附分子(ELAM)-1和血管细胞粘附分子(VCAM)-1以及表皮角质形成细胞上ICAM-1的异常表达。与正常供体皮肤相比,银屑病患者的5个无病变活检组织中有4个具有显著的细胞因子mRNA表达(特别是TNF-α,IL-1 α,IL-1 β,IFN-γ和粒细胞/巨噬细胞集落刺激因子[GM-CSF]的增加较少),这伴随着在相同的4个样本中异常的粘附分子表达。我们得出结论,一个特定的T细胞群体产生1型细胞因子积累在银屑病皮损。此外,临床上无病变皮肤的特征在于真皮和表皮区室中各种细胞因子mRNA的水平增加以及粘附分子表达异常。
As a psoriatic lesion develops at sites of previously uninvolved skin, cytokines and their subsequent induction of various adhesion molecules may play important pathophysiologic roles. To further define the cytokine network in psoriasis, biopsies were obtained from both lesional skin and lesion-free skin of individuals with psoriasis and compared to normal skin biopsies from control subjects. Each biopsy was analyzed using polymerase chain reaction for expression of cytokines and immunostaining to detect adhesion molecules. The results indicate that psoriatic lesions have a type 1 cytokine profile (i.e., interleukin[IL]-2, interferon[IFN]-gamma, and tumor necrosis factor[TNF]-alpha), without a significant component of type 2 cytokines (i.e., IL-4, IL-5, and IL-10) accompanied by aberrant expression of endothelial cell leukocyte adhesion molecule (ELAM)-1 and vascular cell adhesion molecule (VCAM)-1 on dermal endothelial cells, and ICAM-1 on epidermal keratinocytes. Four of five lesion-free biopsies from psoriatic patients had prominent cytokine mRNA expression compared with skin from normal donors (particularly TNF-alpha, IL-1alpha, IL-1beta, with lesser increases in IFN-gamma and granulocyte/macrophage colony-stimulating factor [GM-CSF]), which was accompanied by aberrant adhesion molecule expression in the same four samples. We conclude that a particular T-cell population producing type 1 cytokines accumulates in psoriatic lesions. In addition, clinically lesion-free skin is characterized by increased levels of various cytokine mRNAs, and aberrant adhesion molecule expression in both dermal and epidermal compartments.