Singhera Gurpreet K, Chan Tiffany S, Cheng Jenny Y, Vitalis Timothy Z, Hamann Kimm J, Dorscheid Delbert R
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research/ Critical Care Group, St, Paul's Hospital, University of British Columbia, Vancouver, British Columbia, V6Z-1Y6, Canada.
Respir Res. 2006 May 18;7(1):78. doi: 10.1186/1465-9921-7-78.
Effects of respiratory viral infection on airway epithelium include airway hyper-responsiveness and inflammation. Both features may contribute to the development of asthma. Excessive damage and loss of epithelial cells are characteristic in asthma and may result from viral infection.
To investigate apoptosis in Adenoviral-infected Guinea pigs and determine the role of death receptor and ligand expression in the airway epithelial response to limit viral infection.
Animal models included both an Acute and a Chronic Adeno-infection with ovalbumin-induced airway inflammation with/without corticosteroid treatment. Isolated airway epithelial cells were cultured to study viral production after infection under similar conditions. Immunohistochemistry, western blots and viral DNA detection were used to assess apoptosis, death receptor and TRAIL expression and viral release.
In vivo and in vitro Adeno-infection demonstrated different apoptotic and death receptors (DR) 4 and 5 expression in response to corticosteroid exposure. In the Acute Adeno-infection model, apoptosis and DR4/5 expression was coordinated and were time-dependent. However, in vitro Acute viral infection in the presence of corticosteroids demonstrated delayed apoptosis and prolonged viral particle production. This reduction in apoptosis in Adeno-infected epithelial cells by corticosteroids exposure induced a prolonged virus production via both DR4 and TRAIL protein suppression. In the Chronic model where animals were ovalbumin-sensitized/challenged and were treated with corticosteroids, apoptosis was reduced relative to adenovirus-infected or corticosteroid alone.
Our data suggests that apoptosis of infected cells limits viral production and may be mediated by DR4/5 and TRAIL expression. In the Acute model of Adeno-infection, corticosteroid exposure may prolong viral particle production by altering this apoptotic response of the infected cells. This results from decreased DR4 and TRAIL expression. In the Chronic model treated with corticosteroids, a similar decreased apoptosis was observed. This data suggests that DR and TRAIL modulation by corticosteroids may be important in viral infection of airway epithelium. The prolonged virus release in the setting of corticosteroids may result from reduced apoptosis and suppressed DR4/TRAIL expression by the infected cells.
呼吸道病毒感染对气道上皮的影响包括气道高反应性和炎症。这两种特征都可能促使哮喘的发生。上皮细胞的过度损伤和丢失是哮喘的特征，可能由病毒感染引起。
研究腺病毒感染豚鼠的细胞凋亡情况，并确定死亡受体和配体表达在气道上皮限制病毒感染反应中的作用。
动物模型包括急性和慢性腺病毒感染，伴有或不伴有皮质类固醇治疗的卵清蛋白诱导的气道炎症。分离气道上皮细胞进行培养，以研究在类似条件下感染后的病毒产生情况。采用免疫组织化学、蛋白质印迹法和病毒DNA检测来评估细胞凋亡、死亡受体和肿瘤坏死因子相关凋亡诱导配体（TRAIL）表达以及病毒释放。
体内和体外腺病毒感染显示，在暴露于皮质类固醇时，细胞凋亡和死亡受体4和5的表达有所不同。在急性腺病毒感染模型中，细胞凋亡和死亡受体4/5的表达是协同的且呈时间依赖性。然而，在皮质类固醇存在的情况下进行体外急性病毒感染，显示细胞凋亡延迟且病毒颗粒产生时间延长。皮质类固醇暴露使腺病毒感染的上皮细胞凋亡减少，通过抑制死亡受体4和TRAIL蛋白，导致病毒产生时间延长。在慢性模型中，动物经卵清蛋白致敏/激发并接受皮质类固醇治疗，相对于单独感染腺病毒或单独使用皮质类固醇，细胞凋亡减少。
我们的数据表明，受感染细胞的凋亡限制了病毒产生，可能由死亡受体4/5和TRAIL表达介导。在急性腺病毒感染模型中，皮质类固醇暴露可能通过改变受感染细胞的这种凋亡反应来延长病毒颗粒产生时间。这是由于死亡受体4和TRAIL表达减少所致。在用皮质类固醇治疗的慢性模型中，观察到类似的细胞凋亡减少情况。该数据表明，皮质类固醇对死亡受体和TRAIL的调节在气道上皮病毒感染中可能很重要。在皮质类固醇存在的情况下病毒释放时间延长，可能是由于受感染细胞凋亡减少和死亡受体4/肿瘤坏死因子相关凋亡诱导配体表达受抑制所致。
