Popov Aleksandrov Aleksandra, Mirkov Ivana, Demenesku Jelena, Ninkov Marina, Zolotarevski Lidija, Kataranovski Dragan, Kataranovski Milena
Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia.
Institute of Pathology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
Food Chem Toxicol. 2015 Jan;75:94-103. doi: 10.1016/j.fct.2014.11.010. Epub 2014 Nov 20.
Genetic factors are among the most important determinants of susceptibility to induction of allergic contact dermatitis. A limited number of studies of experimental contact hypersensitivity (CHS) in animals has shown differences in the severity of CHS; however, the underlying mechanisms are unknown. In this study comparative analysis of CHS to low and high dinitrochlorobenzene (DNCB) doses regimen of sensitization/challenge in inbred Dark Agouti (DA) and Albino Oxford (AO) rats was examined. Basic aspects of draining lymph node (dLN) activity (cellularity, proliferation), proinflammatory (IFN-γ, IL-17) and anti-inflammatory (IL-10) cytokine gene expression and production, as well as IL-12 and IL-23 subunits mRNA expression, were examined in challenge and sensitization phase of CHS reaction. Lower (compared to DA) intensity of CHS in AO rats was associated with lack of (or negligible) dLN responses in challenge phase (ex vivo, hapten- or IL-2-stimulated cell proliferation and proinflammatory cytokine mRNA and production levels) but with lack of changes in IL-10 response. Less pronounced dLN activity of sensitized animals of this strain was observed as well. Higher proliferative activity and more pronounced proinflammatory cytokine response during challenge and sensitization phase suggest these activities as underlying mechanisms of higher susceptibility of DA rats to CHS response to DNCB.
遗传因素是诱导过敏性接触性皮炎易感性的最重要决定因素之一。对动物实验性接触性超敏反应（CHS）的有限研究表明，CHS的严重程度存在差异；然而，其潜在机制尚不清楚。在本研究中，对近交系黑豚鼠（DA）和牛津白化大鼠（AO）在低剂量和高剂量二硝基氯苯（DNCB）致敏/激发方案下的CHS进行了比较分析。在CHS反应的激发和致敏阶段，检测了引流淋巴结（dLN）活性（细胞数量、增殖）、促炎（IFN-γ、IL-17）和抗炎（IL-10）细胞因子基因表达和产生，以及IL-12和IL-23亚基mRNA表达的基本情况。AO大鼠中较低的CHS强度（与DA相比）与激发阶段dLN反应缺失（或可忽略不计）相关（体外，半抗原或IL-2刺激的细胞增殖以及促炎细胞因子mRNA和产生水平），但IL-10反应无变化。该品系致敏动物的dLN活性也不太明显。激发和致敏阶段较高的增殖活性和更明显的促炎细胞因子反应表明，这些活性是DA大鼠对DNCB的CHS反应易感性较高的潜在机制。
