The anti-inflammatory effect of alloferon on UVB-induced skin inflammation through the down-regulation of pro-inflammatory cytokines

The anti-inflammatory effect of alloferon on UVB-induced skin inflammation through the down-regulation of pro-inflammatory cytokines
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DOI:
10.1016/j.imlet.2012.09.005
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发表时间:
2013-01-01
期刊:
影响因子:
4.4
通讯作者:
Lee, Wang Jae
Lee, Wang Jae
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Yejin;Lee, Seung Koo;Lee, Wang Jae

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UVB照射可引起皮肤的生物学变化,调节免疫反应并激活导致皮肤损伤的炎症反应。Alloferon是从实验感染的昆虫丽蝇(Calliphora vicina)的血液中分离出来的,以其在小鼠模型中的抗病毒和抗肿瘤活性而闻名。然而,alloferon抗UVB辐射的作用及其具体机制尚不清楚。在这项研究中,我们研究了alloferon对UVB诱导的皮肤炎症的人角质形成细胞系,HaCaT的影响。RPA和ELISA数据表明,alloferon减少UVB诱导的促炎细胞因子,如IL-1 α,IL-1 β,IL-6和IL-18,在mRNA和蛋白质水平上的生产。进行蛋白质印迹分析以确定alloferon是否调节MAPK信号传导途径,因为MAPK信号传导途径被许多炎症介质和环境应激(包括UVB照射)激活。Alloferon可抑制UVB诱导的p38丝裂原活化蛋白激酶(MAPK)的活化。此外,局部应用alloferon的UVB暴露的无毛小鼠的皮肤显示,alloferon治疗显着抑制在慢性UVB照射的小鼠皮肤上皮厚度的增加。这些发现表明,alloferon不仅对UVB诱导的人类角质形成细胞系HaCaT的炎症,而且对小鼠皮肤具有显着的抗炎作用。(C)2012爱思唯尔有限公司版权所有。
UVB irradiation can induce biological changes in the skin, modulate immune responses and activate inflammatory reactions leading to skin damage. Alloferon, which is isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina, is known for its anti-viral and anti-tumor activities in mice model. However, the effect of alloferon against UVB irradiation and its specific mechanism are still unknown. In this study, we investigated the effect of alloferon on UVB-induced cutaneous inflammation in a human keratinocyte cell line, HaCaT. RPA and ELISA data showed that alloferon decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-1 alpha, IL-1 beta, IL-6 and IL-18, both on the mRNA and protein level. Western blot analysis was done to determine if alloferon regulates the MAPK signaling pathway since the MAPK signaling pathway is activated by numerous inflammatory mediators and environmental stresses including UVB irradiation. Alloferon inhibited the activation of p38 mitogen-activated protein kinase (MAPK) induced by UVB irradiation. Furthermore, the topical application of alloferon on the UVB exposed skin of hairless mice showed that alloferon treatment significantly inhibited an increase in epithelial thickness in chronic UVB-irradiated mouse skin. These findings suggest that alloferon has significant anti-inflammatory effects not only on UVB-induced inflammation in the human keratinocyte cell line, HaCaT, but also on mouse skin. (C) 2012 Elsevier B.V. All rights reserved.