Nikitovic Dragana, Berdiaki Aikaterini, Galbiati Valentina, Kavasi Rafaela-Maria, Papale Angela, Tsatsakis Aristidis, Tzanakakis George N, Corsini Emanuela
Laboratory of Anatomy-Histology-Embryology, School of Medicine, University of Crete, Heraklion, Greece.
Laboratory of Anatomy-Histology-Embryology, School of Medicine, University of Crete, Heraklion, Greece.
Toxicol Lett. 2015 Jan 5;232(1):89-97. doi: 10.1016/j.toxlet.2014.09.026. Epub 2014 Oct 1.
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.
白细胞介素-18（IL-18）已被证明在过敏性接触性皮炎的诱导过程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（DAMPs）的成员之一，已被认为具有引发免疫刺激作用。本研究的目的是检测在接触致敏剂2,4-二硝基氯苯（DNCB）和对苯二胺（PPD）刺激后，透明质酸（HA）降解在人角质形成细胞IL-18产生中的作用。通过酶联免疫吸附测定（ELISA）测量人角质形成细胞系NCTC2544中IL-18的产生，而通过实时聚合酶链反应（Real-time PCR）和免疫荧光确定HA代谢的变化。两种接触性变应原均能够增强透明质酸酶（HYAL）1和2的表达，从而诱导HA降解。通过HYAL或马兜铃酸预处理调节HA的产生，导致接触性变应原诱导的IL-18产生显著减少。氧化应激似乎是角质形成细胞激活的初始步骤，因为所有后续事件都可以使用抗氧化剂来阻断。这是LMWHA可作为角质形成细胞中DAMP的首个迹象。总之，LMWHA片段是接触致敏过程中导致依赖IL-18反应的重要介质。
