Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes
Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes
复制标题
DOI：
10.1016/j.toxlet.2014.09.026
复制
发表时间：
2015-01-05
影响因子：
3.5
通讯作者：
Corsini, Emanuela
中科院分区：
文献类型：
--
作者：
Nikitovic, Dragana;Berdiaki, Aikaterini;Corsini, Emanuela
白细胞介素-18（IL-18）已被证明在过敏性接触性皮炎的诱导中起关键的近端作用。低分子量透明质酸（LMWHA）是一种内源性分子，也是所谓的损伤相关分子模式（DAMP）的成员，已被认为可引起免疫刺激作用。本研究的目的是检查透明质酸（HA）降解的作用，在人角质形成细胞的IL-18的生产与接触致敏剂2，4-二硝基氯苯（DNCB）和PPD刺激后。通过ELISA测定人角质形成细胞系NCTC 2544中IL-18的产生，而通过实时PCR和免疫荧光测定HA代谢的变化。两种接触性过敏原都能够增强透明质酸酶（HYAL）1和2的表达，诱导HA降解。HA生产的调制，HYAL或马兜铃酸预处理，导致接触过敏原诱导的IL-18的生产显着减少。氧化应激似乎是KC激活的初始步骤，因为所有事件的后果都可以使用抗氧化剂阻断。这是LMWHA可以在角质形成细胞中充当DAMP的第一个迹象。总之，LMWHA片段是导致IL-18依赖性反应的接触致敏过程中的重要介质。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Interleukin-18 (IL-18) has been shown to play a key proximal role in the induction of allergic contact dermatitis. Low molecular weight hyaluronan (LMWHA), an endogenous molecule and a member of the so-called damage associated molecular patterns (DAMPs), has been suggested to elicit immune-stimulatory effects. The purpose of this study was to examine the role of hyaluronan (HA) degradation in IL-18 production in human keratinocytes following stimulation with the contact sensitizers 2,4-dinitrochlorobenzene (DNCB) and PPD. IL-18 production in the human keratinocyte cell line NCTC2544 was measured by ELISA, whereas changes in HA metabolism were determined by Real-time PCR and immunofluorescence. Both contact allergens were able to enhance hyaluronidase (HYAL) 1 and 2 expression inducing HA degradation. Modulation of HA production, by HYAL or aristolochic acid pre-treatment, resulted in a significant reduction of contact allergen-induced IL-18 production. Oxidative stress appears to be the initial step in KC activation, as all the sequels of events can be blocked using antioxidants. This is the first indication that LMWHA can act as a DAMP in keratinocytes. In conclusion LMWHA fragments are important mediators in the process of contact sensitisation leading to IL-18 dependent responses. (C) 2014 Elsevier Ireland Ltd. All rights reserved.