title: The antioxidant resveratrol down-regulates inflammation in an in-vitro model of Pseudomonas aeruginosa infection of lung epithelial cells.
abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that can cause severe pulmonary infection in immunocompromized individuals. During the infectious process, P. aeruginosa provokes a potent inflammatory response and induces the release of reactive oxygen species (ROS). Cells undergo oxidative stress when cellular antioxidants are unable to effectively scavenge and detoxify ROS, resulting in lung damage. Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenolic compound with recognized antioxidant effects. We hypothesized that owing to its antioxidant activities, resveratrol can attenuate an inflammatory response in P. aeruginosa-infected cells. Lung epithelial A549 cells were pre-treated with 100 μmol/L of resveratrol for 5 h, followed by infection with P. aeruginosa. Intracellular ROS generation was used as an indicator of P. aeruginosa-induced oxidative stress, and cell surface expression of Fas receptor and activation of caspases-3 and -7 as indicators of apoptosis. We also measured the surface expression of intercellular adhesion molecule (ICAM)-1 and enzymes related to inflammation and redox signaling. Resveratrol significantly reduced ROS generation, ICAM-1, and human beta-defensin-2 expression, as well as the markers of apoptosis in A549 cells infected with P. aeruginosa, and up-regulated glutathione peroxidase, suggesting its potential therapeutic role in protecting the lungs against the deleterious effects of P. aeruginosa infection.
authors.affiliation: Biology Department, Lakehead University, Thunder Bay, ON, Canada.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Cerqueira
authors.forename: Neelam
authors.initials: N
authors.lastname: Khaper
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Lees
authors.forename: Marina
authors.initials: M
authors.lastname: Ulanova
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol