Fukuoka M, Ogino Y, Sato H, Ohta T, Komoriya K, Nishioka K, Katayama I
Teijin Institute for Bio-Medical Research, Tokyo, Japan.
Br J Dermatol. 1998 Jan;138(1):63-70. doi: 10.1046/j.1365-2133.1998.02027.x.
The chemokine RANTES is a chemoattractant for eosinophils, T lymphocytes of memory phenotype and monocytes, suggesting that it plays an important part in chronic inflammatory and allergic diseases. In various types of cells, RANTES production is markedly induced by tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in combination. Psoriasis vulgaris is a chronic cutaneous inflammatory disease. Cytokines and chemokines produced by T cells and epidermal keratinocytes, such as interleukin (IL) 8, are involved in the pathogenesis of psoriasis. T-cell clones obtained from psoriatic skin have been shown to produce the Th1 cytokine IFN-gamma. In addition, abnormal expression of proinflammatory cytokines including TNF-alpha has been observed in psoriatic lesions. These reports led us to hypothesis that psoriatic skin could provide epidermal keratinocytes with TNF-alpha and IFN-gamma, so that keratinocytes could produce RANTES. In this study, we addressed the question as to whether RANTES was involved in psoriasis vulgaris. Immunohistochemistry of skin biopsies showed RANTES was present in the intercellular spaces between epidermal keratinocytes, in the fully developed lesions from the middle to the edge of psoriatic plaques, but not in the perilesional uninvolved and healthy control skin. Further, we confirmed the production of RANTES, together with IL-8, by cultured normal human epidermal keratinocytes, using an enzyme-linked immunosorbent assay. Stimulation with TNF-alpha and IFN-gamma in combination synergistically increased the RANTES production in this system. These results clearly demonstrate the expression of RANTES in psoriatic lesions and suggest the involvement of this chemokine in the outcome of cutaneous inflammatory diseases. Tacalcitol (1 alpha,24(R)-dihydroxyvitamin D3), an active vitamin D3 analogue, inhibited RANTES and IL-8 production in cultured normal epidermal keratinocytes. This result indicates that active vitamin D3 is effective in the regulation of chemokine production by epidermal keratinocytes, which may partly account for its action as an antipsoriatic drug.
趋化因子RANTES是嗜酸性粒细胞、记忆表型T淋巴细胞和单核细胞的化学引诱剂，这表明它在慢性炎症和过敏性疾病中起重要作用。在各种类型的细胞中，RANTES的产生可被肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ联合显著诱导。寻常型银屑病是一种慢性皮肤炎症性疾病。T细胞和表皮角质形成细胞产生的细胞因子和趋化因子，如白细胞介素（IL）8，参与了银屑病的发病机制。已证明从银屑病皮肤中获得的T细胞克隆可产生Th1细胞因子IFN-γ。此外，在银屑病皮损中观察到包括TNF-α在内的促炎细胞因子的异常表达。这些报道使我们推测，银屑病皮肤可能为表皮角质形成细胞提供TNF-α和IFN-γ，从而使角质形成细胞能够产生RANTES。在本研究中，我们探讨了RANTES是否参与寻常型银屑病。皮肤活检的免疫组织化学显示，在银屑病斑块中部至边缘的完全发展的皮损中，RANTES存在于表皮角质形成细胞之间的细胞间隙中，但在皮损周围未受累皮肤和健康对照皮肤中不存在。此外，我们使用酶联免疫吸附测定法证实了培养的正常人表皮角质形成细胞可产生RANTES以及IL-8。在该系统中，TNF-α和IFN-γ联合刺激可协同增加RANTES的产生。这些结果清楚地证明了RANTES在银屑病皮损中的表达，并提示这种趋化因子参与了皮肤炎症性疾病的发生发展。他骨化醇（1α,24(R)-二羟基维生素D3），一种活性维生素D3类似物，可抑制培养的正常人表皮角质形成细胞中RANTES和IL-8的产生。这一结果表明活性维生素D3在调节表皮角质形成细胞趋化因子产生方面是有效的，这可能部分解释了其作为抗银屑病药物的作用机制。
