Ravelli Katherine G, Santos Graziella D, Dos Santos Nilton B, Munhoz Carolina D, Azzi-Nogueira Deborah, Campos Ana Carolina, Pagano Rosana L, Britto Luiz R, Hernandes Marina S
Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil.
Department of Pharmacology, University of São Paulo, São Paulo, Brazil.
Transl Neurosci. 2019 Mar 26;10:1-9. doi: 10.1515/tnsci-2019-0001. eCollection 2019.
Multiple sclerosis (MS) is an inflammatory disease of the CNS, characterized by demyelination, focal inflammatory infiltrates and axonal damage. Oxidative stress has been linked to MS pathology. Previous studies have suggested the involvement of NADPH oxidase 2 (Nox2), an enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the MS pathogenesis. The mechanisms of Nox2 activation on MS are unknown. The purpose of this study was to investigate the effect of Nox2 deletion on experimental autoimmune encephalomyelitis (EAE) onset and severity, on astrocyte activation as well as on pro-inflammatory and anti-inflammatory cytokine induction in striatum and motor cortex.
Subcutaneous injection of MOG35-55 emulsified with complete Freund's adjuvant was used to evaluate the effect of Nox2 depletion on EAE-induced encephalopathy. Striatum and motor cortices were isolated and evaluated by immunoblotting and RT-PCR.
Nox2 deletion resulted in clinical improvement of the disease and prevented astrocyte activation following EAE induction. Nox2 deletion prevented EAE-induced induction of pro-inflammatory cytokines and stimulated the expression of the anti-inflammatory cytokines IL-4 and IL-10.
Our data suggest that Nox2 is involved on the EAE pathogenesis. IL-4 and IL-10 are likely to be involved on the protective mechanism observed following Nox2 deletion.
多发性硬化症（MS）是一种中枢神经系统的炎症性疾病，其特征为脱髓鞘、局灶性炎症浸润和轴突损伤。氧化应激与MS病理过程相关。先前的研究表明，烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（Nox2）参与了MS的发病机制，该酶催化氧气还原以产生活性氧。Nox2在MS中激活的机制尚不清楚。本研究的目的是探讨Nox2缺失对实验性自身免疫性脑脊髓炎（EAE）发病及严重程度、对星形胶质细胞激活以及对纹状体和运动皮层中促炎和抗炎细胞因子诱导的影响。
皮下注射用完全弗氏佐剂乳化的MOG35-55，以评估Nox2缺失对EAE诱导的脑病的影响。分离纹状体和运动皮层，通过免疫印迹和逆转录-聚合酶链反应进行评估。
Nox2缺失导致疾病的临床改善，并在EAE诱导后防止星形胶质细胞激活。Nox2缺失阻止了EAE诱导的促炎细胞因子的诱导，并刺激了抗炎细胞因子IL-4和IL-10的表达。
我们的数据表明Nox2参与了EAE的发病机制。IL-4和IL-10可能参与了Nox2缺失后观察到的保护机制。
