title: The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection.
abstract: The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8(+) effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Traboulsi
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Cloutier
authors.affiliation: Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Institut de Pharmacologie de Sherbrooke, Sherbooke, Québec, Canada.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Boyapelly
authors.affiliation: Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Institut de Pharmacologie de Sherbrooke, Sherbooke, Québec, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Bonin
authors.affiliation: Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Institut de Pharmacologie de Sherbrooke, Sherbooke, Québec, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Marsault
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada.
authors.forename: André M
authors.initials: AM
authors.lastname: Cantin
authors.affiliation: Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada Martin.Richter@USherbrooke.ca.
authors.forename: Martin V
authors.initials: MV
authors.lastname: Richter
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000254:growth & development; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; C503460:Ccl5 protein, mouse; D047188:Chalcones; D018946:Chemokine CCL5; D053583:Interleukin-1beta; D015850:Interleukin-6; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D007371:Interferon-gamma; C040920:isoliquiritigenin