Cutaneous immune responses to niacin in photosensitivity

糙皮病是一种光敏性综合征，其特征为三个“D”：腹泻、皮炎和烟酸缺乏引起的痴呆。然而，光敏性皮炎的分子机制的标志性异常，这种综合征还不清楚。在这里，我们表明，增强小鼠的光敏性诱导治疗与烟酸拮抗剂以及烟酸缺乏的饮食，并与烟酸拮抗剂，这表明这是一个糙皮病模型治疗引起的严重腹泻与体重减轻。有趣的是，烟酸拮抗剂诱导考克斯-2和PGE合成（Ptges）mRNA的表达升高。烟酸拮抗剂治疗诱导的光敏性通过考克斯抑制剂、Ptges缺乏或EP 4受体信号传导阻断而减轻。与小鼠中的上述发现一致，糙皮病患者的皮肤病变的分析证实了Ptges的表达增强。总之，这些发现表明烟酸缺乏导致糙皮病中光敏性的发展，其是由响应于增加的PGE产生的通过EP 4的信号传导介导的。

Pellagra is a photosensitivity syndrome characterized by three “D’s”: diarrhea, dermatitis and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis underlying the hallmark abnormalities of this syndrome are unclear. Here we show that enhanced photosensitivity in mice was induced by treatment with a niacin antagonist as well as niacin-deficient diets, and that severe diarrhea with weight loss was induced by treatment with the niacin ntagonist, which suggest that this is a model of pellagra. Intriguingly, the niacin antagonist induced elevated expression of COX-2 and PGE syntheses (Ptges) mRNAs. The niacin antagonist treatment-induced photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. In line with the above findings in mice, analysis of skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Taken together, these findings indicate that niacin deficiency results in the development of photosensitivity in pellagra mediated by signaling through EP4 in response to increased PGE production.