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

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Abstract

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC) Grants 31372418 (G. Liu) and 31201913 (S. Zhang), NSFC Major International Cooperation Project 31210103917 (B. Liu), Huazhong Agricultural University Scientific and Technology Self-Innovation Foundation Program 2012RC011 (G. Liu), and the 948 Project of Chinese Ministry of Agriculture (2015-Z33, GL).

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Authors and Affiliations

  1. Department of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei Province, People’s Republic of China

    Meiping Yan, Make Hou, Jie Liu, Xiaoxiong Wu & Guoquan Liu

  2. Shandong Binzhou Animal Science and Veterinary Medicine Academy, Binzhou, 256600, Shandong Province, People’s Republic of China

    Songlin Zhang

  3. Department of Animal Genetics and Breeding, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei Province, People’s Republic of China

    Bang Liu

  4. Key Lab of Swine Genetics and Breeding and Agricultural Animal Breeding and Reproduction, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei Province, People’s Republic of China

    Bang Liu & Guoquan Liu

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  1. Meiping Yan
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  2. Make Hou
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  3. Jie Liu
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Correspondence to Bang Liu or Guoquan Liu.

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Animal experiments were approved by Animal Care and Use Committee of Hubei Province, China, in accordance with guidelines developed by the China Council on Animal Care and protocol.

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Yan, M., Hou, M., Liu, J. et al. Regulation of iNOS-Derived ROS Generation by HSP90 and Cav-1 in Porcine Reproductive and Respiratory Syndrome Virus-Infected Swine Lung Injury. Inflammation 40, 1236–1244 (2017). https://doi.org/10.1007/s10753-017-0566-9

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