Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.
Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.
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DOI：
10.1016/j.jid.2017.01.007
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Man MQ
中科院分区：
文献类型：
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作者：
Hu L;Mauro TM;Dang E;Man G;Zhang J;Lee D;Wang G;Feingold KR;Elias PM;Man MQ
尽管老年人群缺乏明显的炎症或其他临床症状，但他们的血清细胞因子和 C 反应蛋白水平通常会升高。然而，与年龄相关的全身炎症的起源尚不清楚。我们之前的研究表明，表皮功能异常会引发皮肤炎症，并且由于本质上老化的皮肤表现出渗透性屏障稳态受损以及角质层水合作用减少，因此我们在此假设表皮功能障碍可能导致老年人血清细胞因子升高。我们的结果首先表明，年轻小鼠表皮通透性屏障的急性破坏不仅导致皮肤细胞因子 mRNA 表达迅速增加，而且导致血清细胞因子水平增加。其次，在其他方面正常的老年小鼠（> 12 个月）中，皮肤和血清中的细胞因子水平均有所增加。第三，表皮中的 TNFα 和淀粉样蛋白 A mRNA 水平增加，但肝脏中并未增加，同时血清细胞因子水平也显着升高。第四，渗透性屏障的破坏导致正常和无胸腺小鼠的表皮和血清细胞因子水平相似升高，这表明T细胞在表皮功能障碍引起的皮肤和血清炎症细胞因子升高中所起的作用可以忽略不计。第五，表皮功能的纠正不仅显着降低了皮肤中的细胞因子水平，而且还显着降低了老年小鼠血清中的细胞因子水平。总之，这些结果表明，按时间顺序老化的皮肤表皮功能的持续异常导致炎症细胞因子的血清水平升高，可能使老年人易于随后发生或恶化慢性炎症性疾病。
Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis, as well as reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice led not only to a rapid increase in cutaneous cytokine mRNA expression, but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increased in otherwise normal, aged mice (>12 months). Third, expression of TNFα and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with significant elevations in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting the T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin, but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders.