Nickoloff B J, Karabin G D, Barker J N, Griffiths C E, Sarma V, Mitra R S, Elder J T, Kunkel S L, Dixit V M
Department of Pathology, University of Michigan Medical School, Ann Arbor.
Am J Pathol. 1991 Jan;138(1):129-40.
The importance of immunologic mechanisms in psoriasis has been deduced from the ability of immunosuppressive therapies to ameliorate this common and chronic skin disease. Certainly the histology of psoriatic lesions suggests a dialogue between the hyperplastic keratinocytes and infiltrating T lymphocytes and macrophages. To begin dissecting the cytokine network involved in the pathophysiology of psoriasis, the location, in both epidermal and dermal compartments, of tumor necrosis factor-alpha, interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha at the protein and/or mRNA levels were identified. Tumor necrosis factor-alpha was selected as a potentially key regulatory cytokine, first because it induces cultured keratinocyte interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha production, and second because intercellular adhesion molecule-1 expression by keratinocytes in psoriatic epidermis had been identified previously. Using immunohistochemical localization, tumor necrosis factor-alpha was identified in 12 psoriatic lesions as intense and diffuse expression by dermal dendrocytes (macrophages) in the papillary dermis (without significant staining of endothelial cells, mast cells, or dermal Langerhans cells), and focally by keratinocytes and intraepidermal Langerhans cells. Functional interaction between the dermal dendrocytes and keratinocytes was suggested by the presence of interleukin-8 expression of suprabasal keratinocytes immediately above the tumor necrosis factor-alpha-positive dermal dendrocytes. Interleukin-8 mRNA and transforming growth factor-alpha mRNA were detectable in the epidermal roof of psoriatic lesions, but neither was detectable at the protein or mRNA levels in any normal skin specimens. Treatment of cultured human keratinocytes with phorbol ester (which experimentally produces psoriasiform changes on mouse skin) or tumor necrosis factor-alpha also increased interleukin-8 and transforming growth factor-alpha mRNAs. Further elucidation of the cellular and molecular basis for the genesis and evolution of psoriasis will provide the framework for a better evaluation of the cause and treatment of this skin disease.
免疫机制在银屑病中的重要性已从免疫抑制疗法改善这种常见慢性皮肤病的能力中推断出来。当然，银屑病皮损的组织学提示增生的角质形成细胞与浸润的T淋巴细胞和巨噬细胞之间存在相互作用。为了剖析参与银屑病病理生理学的细胞因子网络，确定了肿瘤坏死因子-α、白细胞介素-8、细胞间黏附分子-1和转化生长因子-α在表皮和真皮层中蛋白质和/或mRNA水平的定位。肿瘤坏死因子-α被选为潜在的关键调节细胞因子，首先是因为它可诱导培养的角质形成细胞产生白细胞介素-8、细胞间黏附分子-1和转化生长因子-α，其次是因为先前已确定银屑病表皮中的角质形成细胞表达细胞间黏附分子-1。通过免疫组织化学定位，在12个银屑病皮损中发现肿瘤坏死因子-α在乳头真皮中的真皮树突状细胞（巨噬细胞）中呈强烈弥漫性表达（内皮细胞、肥大细胞或真皮朗格汉斯细胞无明显染色），角质形成细胞和表皮内朗格汉斯细胞呈局灶性表达。在肿瘤坏死因子-α阳性的真皮树突状细胞上方的基底上层角质形成细胞中存在白细胞介素-8表达，提示真皮树突状细胞与角质形成细胞之间存在功能相互作用。在银屑病皮损的表皮顶部可检测到白细胞介素-8 mRNA和转化生长因子-α mRNA，但在任何正常皮肤标本中均未在蛋白质或mRNA水平检测到。用佛波酯（实验中可在小鼠皮肤上产生银屑病样变化）或肿瘤坏死因子-α处理培养的人角质形成细胞也会增加白细胞介素-8和转化生长因子-α mRNA。进一步阐明银屑病发生和发展的细胞和分子基础将为更好地评估这种皮肤病的病因和治疗提供框架。
