Oberyszyn T M, Tober K L, Ross M S, Robertson F M
Department of Medical Microbiology/Immunology, The College of Medicine, The Ohio State University, Columbus, USA.
Mol Carcinog. 1998 May;22(1):16-25.
It is now recognized that ultraviolet (UV) radiation is a potent environmental insult capable of interfering with immunity to skin cancers and modifying certain immunologic reactions within both locally irradiated skin and distant, unexposed sites. Exposure to UVB light (290-320 nm) induces a potent cutaneous inflammatory response that involves the infiltration of leukocytes into the dermis as well as the production of proinflammatory cytokines by both resident epidermal keratinocytes and dermal cells. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been shown to be a major mediator of UVB light effects on cutaneous immunity. Recent studies have demonstrated that pentoxifylline (PTX), a xanthine-derived phosphodiesterase inhibitor, has the ability to inhibit synthesis of TNF-alpha. To examine the effects of PTX on UVB-mediated cutaneous inflammation, Skh/hr hairless mice were injected intraperitoneally with either phosphate-buffered saline or 50 microg/g PTX 1 h before exposure to 2240 J/m2 UVB. Reverse transcription-polymerase chain reaction and immunohistochemical techniques were used to demonstrate that 24 h to 1 wk after UVB-light irradiation, PTX inhibited UVB-induced TNF-alpha gene expression, inhibited the increase in epidermal TNF-alpha protein synthesis, blocked the increase in epidermal proliferation observed after exposure to UVB light, and decreased production of myeloperoxidase by neutrophils infiltrating into the dermis. These studies demonstrated that PTX modifies epidermal responses after acute UVB light exposure and suggest that PTX treatment may be used clinically to modulate the deleterious effects of long-term UVB-light irradiation.
现在人们认识到，紫外线（UV）辐射是一种强大的环境侵害因素，能够干扰对皮肤癌的免疫反应，并改变局部照射皮肤和远处未暴露部位的某些免疫反应。暴露于中波紫外线（UVB，290 - 320纳米）会引发强烈的皮肤炎症反应，这涉及白细胞浸润到真皮层，以及驻留的表皮角质形成细胞和真皮细胞产生促炎细胞因子。肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，已被证明是UVB对皮肤免疫作用的主要介质。最近的研究表明，己酮可可碱（PTX），一种黄嘌呤衍生的磷酸二酯酶抑制剂，有能力抑制TNF-α的合成。为了研究PTX对UVB介导的皮肤炎症的影响，在暴露于2240 J/m² 的UVB之前1小时，给无毛Skh/hr小鼠腹腔注射磷酸盐缓冲盐水或50微克/克的PTX。采用逆转录-聚合酶链反应和免疫组织化学技术来证明，在UVB照射后24小时至1周，PTX抑制UVB诱导的TNF-α基因表达，抑制表皮TNF-α蛋白合成的增加，阻止暴露于UVB后观察到的表皮增殖增加，并减少浸润到真皮的中性粒细胞的髓过氧化物酶的产生。这些研究表明，PTX改变急性UVB照射后的表皮反应，并提示PTX治疗可能在临床上用于调节长期UVB照射的有害影响。
