Kim T-B, Kim S Y, Moon K-A, Park C-S, Jang M K, Yun E S, Cho Y S, Moon H-B, Lee K-Y
Division of Allergy, University of Ulsan College of Medicine, Seoul, Korea.
Clin Exp Allergy. 2007 Nov;37(11):1709-19. doi: 10.1111/j.1365-2222.2007.02812.x. Epub 2007 Sep 17.
Asthma can frequently be induced or exacerbated by respiratory viral infections. Oxidative stress might also play an essential role in the pathogenesis of allergic airway diseases, indicating that antioxidant therapy may have a potential effect in controlling allergic airway diseases. Recent studies showed that 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) has the potential ability to modulate NADPH oxidase activity, indicating the antioxidant activity of AICAR. This study investigated the inhibitory effects of AICAR as an anti-inflammatory modulator on allergic airway inflammation in murine animal models.
The anti-inflammatory effects of AICAR were evaluated in two experimental asthma models: (1) an ovalbumin (OVA)-induced experimental asthma model and (2) an OVA plus polyinosinic-polycytidylic acid [poly (I:C)]-induced experimental asthma model to mimic respiratory viral infections. The inhibitory effects of AICAR in poly (I:C)-mediated signalling for NF-kappaB activation and production of TNF-alpha were analysed in vitro.
AICAR was shown to have a marginal inhibitory effect in an OVA-induced asthma model. Interestingly, AICAR significantly attenuated poly (I:C)-induced airway hyperresponsiveness and airway inflammation, as shown by the attenuation of the influx of total inflammatory cells and soluble products into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-5, IL-13, TNF-alpha and IFN-gamma. AICAR also significantly reduced the serum levels of OVA-specific IgE and IgG2a antibodies. Histologic and flow cytometric studies showed that AICAR inhibited poly (I:C)-induced lung inflammation and the infiltration of CD11b+CD11c+ dendritic cells into the lung. Moreover, AICAR effectively inhibited poly (I:C)-mediated activation of NF-kappaB and the production of TNF-alpha.
These findings suggest that AICAR may be a novel immunomodulator with promising beneficial effects for the treatment of respiratory viral infection in airway allergic diseases.
哮喘常由呼吸道病毒感染诱发或加重。氧化应激可能在过敏性气道疾病的发病机制中也起重要作用，这表明抗氧化治疗可能对控制过敏性气道疾病有潜在效果。最近的研究表明，5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）具有调节NADPH氧化酶活性的潜在能力，提示AICAR具有抗氧化活性。本研究在小鼠动物模型中探究了AICAR作为一种抗炎调节剂对过敏性气道炎症的抑制作用。
在两种实验性哮喘模型中评估AICAR的抗炎作用：（1）卵清蛋白（OVA）诱导的实验性哮喘模型和（2）OVA加聚肌苷酸-聚胞苷酸[聚（I:C）]诱导的实验性哮喘模型，以模拟呼吸道病毒感染。在体外分析AICAR对聚（I:C）介导的NF-κB激活信号和肿瘤坏死因子-α（TNF-α）产生的抑制作用。
在OVA诱导的哮喘模型中，AICAR显示出轻微的抑制作用。有趣的是，AICAR显著减轻了聚（I:C）诱导的气道高反应性和气道炎症，如总炎症细胞和可溶性产物流入支气管肺泡灌洗液（如巨噬细胞、嗜酸性粒细胞、白细胞介素-5、白细胞介素-13、TNF-α和干扰素-γ）的减少所示。AICAR还显著降低了OVA特异性免疫球蛋白E（IgE）和免疫球蛋白G2a（IgG2a）抗体的血清水平。组织学和流式细胞术研究表明，AICAR抑制了聚（I:C）诱导的肺部炎症以及CD11b+CD11c+树突状细胞向肺部的浸润。此外，AICAR有效抑制了聚（I:C）介导的NF-κB激活和TNF-α的产生。
这些发现表明，AICAR可能是一种新型免疫调节剂，对气道过敏性疾病中呼吸道病毒感染的治疗具有有前景的有益作用。
