Cutaneous immune responses to niacin in photosensitivity

糙皮病是一种以三个“D”为特征的光敏综合征：腹泻、皮炎和由烟酸缺乏引起的痴呆。然而，光敏性皮炎的分子机制背后的标志异常esta综合征尚不清楚。本研究表明，烟酸拮抗剂和缺乏烟酸的饮食可诱导小鼠光敏性增强，烟酸拮抗剂可诱导小鼠严重腹泻并减轻体重，这表明这是糙皮病的一种模型。有趣的是，烟酸拮抗剂诱导COX-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可通过COX抑制剂、缺乏Ptges或阻断EP4受体信号传导而减轻。与上述在小鼠中的发现一致，对糙皮病患者皮损的分析证实了pges的表达增强。综上所述，这些发现表明烟酸缺乏导致糙皮病光敏性的发展，这是通过信号传导EP4介导的，以响应PGE的增加。

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.