title: Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice.
abstract: Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.
authors.affiliation: Lung Health Research Centre, Department of Pharmacology &Therapeutics, The University of Melbourne, Victoria, Australia.|Department of Molecular Pharmacology, The University of Groningen, Groningen, The Netherlands.
authors.forename: L C
authors.initials: LC
authors.lastname: Oostwoud
authors.affiliation: Lung Health Research Centre, Department of Pharmacology &Therapeutics, The University of Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Gunasinghe
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: H J
authors.initials: HJ
authors.lastname: Seow
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Selemidis
authors.affiliation: Lung Health Research Centre, Department of Pharmacology &Therapeutics, The University of Melbourne, Victoria, Australia.|School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Bozinovski
authors.affiliation: Lung Health Research Centre, Department of Pharmacology &Therapeutics, The University of Melbourne, Victoria, Australia.|School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Vlahos
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage*; D000818:Animals; D001393:Azoles / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity; D054833:Isoindoles; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D000098:Acetophenones; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D012906:Smoke; C042986:ebselen; C056165:acetovanillone