Regulation of iNOS-Derived ROS Generation by HSP90 and Cav-1 in Porcine Reproductive and Respiratory Syndrome Virus-Infected Swine Lung Injury

• DOI: 10.1007/s10753-017-0566-9
• Publication Date: 2017-05-10T04:26:21Z
• Authors: Meiping Yan; Make Hou; Jie Liu; Songlin Zhang; Bang Liu; Xiaoxiong Wu; Guoquan Liu
• Keywords: 0303 health sciences; Nitric Oxide Synthase Type III; Swine; Caveolin 1; Nitric Oxide Synthase Type II; Lung Injury; Nitric Oxide; 3. Good health; 03 medical and health sciences; Animals; Porcine respiratory and reproductive syndrome virus; HSP90 Heat-Shock Proteins; Reactive Oxygen Species

In the lungs, endothelial nitric oxide synthase (eNOS) is usually expressed in endothelial cells and inducible nitric oxide synthase (iNOS) is mainly expressed in alveolar macrophages and epithelial cells. Both eNOS and iNOS are involved in lung inflammation. While they play several roles in lung inflammation formation and resolution, their expression and activity are also regulated by inflammatory factors. Their expression relationship in virus infection-induced lung injury is not well addressed. In this report, we analyzed expression of both eNOS and iNOS, the production of nitric oxide (NO) and reactive oxygen species (ROS), and expression of their associated regulatory proteins, heat shock protein 90 (HSP90) and caveolin-1 (Cav-1), in a swine lung injury model induced by porcine reproductive and respiratory syndrome virus (PRRSV) infection. The combination of upregulation of iNOS and downregulation of eNOS was observed in both natural and experimental PRRSV-infected lungs, while the combination is much enhanced in natural infected lungs. While NO production is much reduced in both infections, ROS was enhanced only in natural infected lungs. Moreover, HSP90 is increased in both natural and experimental infection and less Cav-1 expressed was observed only in the natural PRRSV-infected lungs. Therefore, the increased ROS generation is likely due to the increased iNOS and its unbalanced regulation by HSP90 and Cav-1, and it also likely causes higher endothelial dysfunction in clinical PRRSV-infected lungs.