Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in
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ORIGINAL ARTICLE
Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in mice Wei Liu 1 & Xiaojuan Ren 2 & Qian Wang 2 & Yan Zhang 2 & Junfeng Du 3 Received: 1 July 2020 / Accepted: 24 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift and drug resistance. Poly (ADPribose) polymerases (PARPs) are considered effective therapeutic targets of acute lung inflammatory injury. This study aimed to explore the effects of PARP-1 inhibitor olaparib on IAV-induced lung injury and the underlying mechanisms. Male wild-type C57BL/6 mice were intranasally infected with IAV strain H1N1 to mimic pneumonia experimentally. Olaparib at different doses was intraperitoneally injected 2 days before and 5 consecutive days after virus stimulation. On day 6 post-infection, lung tissues as well as bronchoalveolar lavage fluid (BALF) were sampled for histological and biochemical analyses. Olaparib increased the survival rate of IAV mice dose-dependently. Olaparib remarkably reduced IAV mRNA expression, myeloperoxidase (MPO) level, and inflammatory cell infiltration in IAV lungs. Moreover, olaparib significantly reduced the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, and IL-4 and increased IL-10 in IAV lungs. Also, olaparib efficiently reduced IL-6, monocyte chemotactic protein (MCP)-1, granulocyte colony-stimulating factor (G-CSF), TNF-α, chemokine (C– X–C motif) ligand (CXCL)1, CXCL10, chemokine (C–C motif) ligand (CCL)3, and regulated on activation, normal T cell expressed and secreted (RANTES) release in IAV BALF. Olaparib decreased PARylated protein content and p65, IκBα phosphorylation in IAV lung tissues. This study successfully constructed the pneumonia murine model using IAV. Olaparib decreased IAV-induced mortality in mice, lung injury, and cytokine production possibly via modulation of PARP-1/NF-κB axis. Keywords Influenza A virus . PARP . Olaparib . Pneumonia . Cytokines
Introduction Influenza is an acute infectious disease affecting respiratory tracts accompanied with different clinical manifestations ranging from wild to lethal. Influenza causes seasonal, unpredictable Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10096-020-04020-5) contains supplementary material, which is available to authorized users. * Wei Liu [email protected] 1
Department of Clinical Laboratory, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou 061001, Hebei, China
2
Department of Infectious Diseases Medicine, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou 061001, Hebei, China
3
Department of Respiratory and Critical Care Medicine, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou 061001, Hebei, China
epidemics and it is now one of the major public health concerns worldwide [1, 2]. According to the report of the World Health Orga
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