PDF(Pubmed)
Abstract：
Actinic lentigines (AL) or age spots, are skin hyperpigmented lesions associated with age and chronic sun exposure. To better understand the physiopathology of AL, we have characterized the inflammation response in AL of European and Japanese volunteers. Gene expression profile showed that in both populations, 10% of the modulated genes in AL versus adjacent non lesional skin (NL), i.e. 31 genes, are associated with inflammation/immune process. A pro-inflammatory environment in AL is strongly suggested by the activation of the arachidonic acid cascade and the plasmin pathway leading to prostaglandin production, along with the decrease of anti-inflammatory cytokines and the identification of inflammatory upstream regulators. Furthermore, in line with the over-expression of genes associated with the recruitment and activation of immune cells, immunostaining on skin sections revealed a significant infiltration of CD68+ macrophages and CD4+ T-cells in the dermis of AL. Strikingly, investigation of infiltrated macrophage subsets evidenced a significant increase of pro-inflammatory CD80+/CD68+ M1 macrophages in AL compared to NL. In conclusion, a chronic inflammation, sustained by pro-inflammatory mediators and infiltration of immune cells, particularly pro-inflammatory M1 macrophages, takes place in AL. This pro-inflammatory loop should be thus broken to normalize skin and improve the efficacy of age spot treatment.
摘要：
光化性雀斑（AL）或老年斑，是与年龄和慢性日晒相关的皮肤色素沉着病变。为了更好地了解AL的病理生理学,我们对欧洲和日本志愿者AL的炎症反应进行了表征。基因表达谱显示，在两个种群中，与邻近的非皮损皮肤(NL)相比，AL中10%的受调节基因，即31个基因，与炎症/免疫过程有关。花生四烯酸级联的激活和纤溶酶途径导致前列腺素产生，强烈提示AL中的促炎环境。随着抗炎细胞因子的减少和炎症上游调节因子的鉴定。此外，与免疫细胞募集和激活相关基因的过度表达相一致，皮肤切片上的免疫染色显示AL真皮中CD68巨噬细胞和CD4T细胞的显着浸润。引人注目的是，对浸润巨噬细胞亚群的研究表明,与NL相比,AL中促炎CD80+/CD68+M1巨噬细胞显著增加.总之,慢性炎症,由促炎介质和免疫细胞浸润维持，特别是促炎M1巨噬细胞，发生在AL。因此，应该打破这种促炎循环以使皮肤正常化并改善老年斑治疗的功效。
