Unknown

Dataset Information

0

Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in mice.


ABSTRACT: Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift and drug resistance. Poly (ADP-ribose) 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)-1?, tumor necrosis factor (TNF)-?, interferon (IFN)-?, 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-?, 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, I?B? 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-?B axis.

PROVIDER: S-EPMC7456638 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC6094359 | BioStudies
2017-01-01 | S-EPMC5587948 | BioStudies
1000-01-01 | S-EPMC6338318 | BioStudies
| S-EPMC4677544 | BioStudies
2017-01-01 | S-EPMC5218563 | BioStudies
2015-01-01 | S-EPMC4433232 | BioStudies
2016-01-01 | S-EPMC4753462 | BioStudies
| S-EPMC7499199 | BioStudies
2020-01-01 | S-EPMC7607282 | BioStudies
| S-EPMC4567647 | BioStudies