Imiquimod-induced interleukin-1 alpha stimulation improves barrier homeostasis in aged murine epidermis.

Imiquimod-induced interleukin-1 alpha stimulation improves barrier homeostasis in aged murine epidermis.
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咪喹莫特诱导的白细胞介素 1 α 刺激可改善老年小鼠表皮的屏障稳态。

DOI:
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发表时间:
2004
影响因子:
6.5
通讯作者:
R. Ghadially
R. Ghadially
中科院分区:
医学1区
文献类型:
--
作者:
C. Barland;Elizabeth Zettersten;Barbara S Brown;Jianqin Ye;P. Elias;R. Ghadially

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响应于老年哺乳动物的渗透性屏障的急性破坏,屏障恢复的能力减弱,类似于其他老年器官在受到压力时的情况。急性屏障破坏增加表皮细胞因子的水平,并且细胞因子是角质形成细胞有丝分裂发生以及皮外组织中脂质合成的已知调节剂。老化皮肤中缓慢的屏障恢复的基础是白细胞介素-1细胞因子家族及其受体的mRNA和蛋白质水平的降低。为了进一步阐明白细胞介素-1家族的细胞因子在屏障修复反应中的作用,用局部咪喹莫特应用刺激衰老小鼠皮肤中的细胞因子产生。咪喹莫特加速老化和年轻皮肤急性损伤后的屏障恢复。这些功能结果与局部给予咪喹莫特后表皮中白细胞介素-1 α产生增加暂时相关。此外,皮内注射白细胞介素-1 α可加速老年小鼠的屏障恢复。最后,我们发现,白细胞介素-1 α添加到培养的人角质形成细胞刺激表皮脂质合成。这些研究为减少的白细胞介素-1 α信号传导在老年皮肤渗透性屏障功能下降中的作用提供了进一步的证据,并指出了细胞因子增强在老年人屏障功能障碍中的潜在用途。
In response to acute disruption of the permeability barrier of aged mammals there is a diminished capacity for barrier recovery, analogous to other aged organs when stressed. Acute barrier disruption increases levels of epidermal cytokines, and cytokines are known regulators of keratinocyte mitogenesis, as well as lipid synthesis in extracutaneous tissues. Underlying the sluggish barrier recovery in aged skin are diminished mRNA and protein levels for the interleukin-1 cytokine family, and its receptors. To further elucidate the role of the interleukin-1 family of cytokines in the barrier repair response, cytokine production was stimulated in aged murine skin with topical imiquimod application. Imiquimod accelerated barrier recovery after acute insults to aged and young skin. These functional results correlated temporally with increased interleukin-1 alpha production in the epidermis following topical imiquimod administration to murine skin. Furthermore, intracutaneous injections of interleukin-1 alpha accelerated barrier recovery in aged mice. Finally, we showed that interleukin-1 alpha added to cultured human keratinocytes stimulates epidermal lipid synthesis. These studies provide further evidence for the role of reduced interleukin-1 alpha signaling in the decline of permeability barrier function in aged skin, and point to the potential use of cytokine augmentation in barrier dysfunction of the aged.
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