Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer.
Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer.
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DOI：
10.1016/j.plipres.2016.03.004
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发表时间：
2016-07
影响因子：
13.6
通讯作者：
Ullrich SE
中科院分区：
文献类型：
--
作者：
Damiani E;Ullrich SE
炎症的脂质介质在包括皮肤癌在内的几种疾病中发挥重要作用，皮肤癌是工业化世界中发现的最普遍的癌症类型。紫外线（UV）辐射是一种完全致癌的物质，是皮肤癌的主要原因。紫外线辐射也是一种有效的免疫抑制剂，紫外线诱导的免疫抑制是众所周知的皮肤癌诱导的危险因素。在这一过程中一个重要的介质是甘磷酸胆碱- 1-烷基-2-乙酰- asn -甘油-3-磷酸胆碱，通常被称为血小板活化因子（PAF）。PAF是由角质形成细胞在多种刺激下产生的，并通过与多种细胞上表达的单一特异性g蛋白偶联受体（PAF- r）结合来发挥其生物学作用。这篇综述将试图描述这种脂质介质是如何参与将免疫抑制信号从皮肤传递到免疫系统的，从角质形成细胞的产生开始，到它在体内激活肥大细胞迁移的作用，以及最终导致免疫抑制的机制。最近的研究发现其在调节DNA修复和激活表观遗传机制中的作用，进一步明确了这种生物活性脂质的重要性，它可能作为连接环境（UVB辐射）与免疫系统和表观基因组的关键分子介质。
Lipid mediators of inflammation play important roles in several diseases including skin cancer, the most prevalent type of cancer found in the industrialized world. Ultraviolet (UV) radiation is a complete carcinogen and is the primary cause of skin cancer. UV radiation is also a potent immunosuppressive agent, and UV-induced immunosuppression is a well-known risk factor for skin cancer induction. An essential mediator in this process is the glyercophosphocholine 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine commonly referred to as platelet-activating factor (PAF). PAF is produced by keratinocytes in response to diverse stimuli and exerts its biological effects by binding to a single specific G-protein-coupled receptor (PAF-R) expressed on a variety of cells. This review will attempt to describe how this lipid mediator is involved in transmitting the immunosuppressive signal from the skin to the immune system, starting from its production by keratinocytes, to its role in activating mast cell migration in vivo, and to the mechanisms involved that ultimately lead to immune suppression. Recent findings related to its role in regulating DNA repair and activating epigenetic mechanisms, further pinpoint the importance of this bioactive lipid, which may serve as a critical molecular mediator that links the environment (UVB radiation) to the immune system and the epigenome.