title: Proresolving Action of Docosahexaenoic Acid Monoglyceride in Lung Inflammatory Models Related to Cystic Fibrosis.
abstract: Cystic fibrosis (CF) is a hereditary, chronic disease of the exocrine glands, characterized by the production of viscid mucus that obstructs the pancreatic ducts and bronchi, leading to infection and fibrosis. ω3 fatty acid supplementations are known to improve the essential fatty acid deficiency as well as reduce inflammation in CF. The objective of this study was to determine the effects of docosahexaenoic acid monoacylglyceride (MAG-DHA) on mucin overproduction and resolution of airway inflammation in two in vitro models related to CF. Isolated human bronchi reverse permeabilized with CF transmembrane conductance regulator (CFTR) silencing (si) RNA and stable Calu3 cells expressing a short hairpin (sh) RNA directed against CFTR (shCFTR) were used. Lipid analyses revealed that MAG-DHA increased DHA/arachidonic acid (AA) ratio in shCFTR Calu-3 cells. MAG-DHA treatments, moreover, resulted in a decreased activation of Pseudomonas aeruginosa LPS-induced NF-κB in CF and non-CF Calu-3 cells. Data also revealed a reduction in MUC5AC, IL-6, and IL-8 expression levels in MAG-DHA-treated shCFTR cells stimulated, or not, with LPS. Antiinflammatory properties of MAG-DHA were also investigated in a reverse-permeabilized human bronchi model with CFTR siRNA. After MAG-DHA treatments, messenger RNA transcript levels for MUC5AC, IL-6, and IL-8 were markedly reduced in LPS-treated CFTR siRNA bronchi. MAG-DHA displays antiinflammatory properties and reduces mucin overexpression in Calu-3 cells and human bronchi untreated or treated with P. aeruginosa LPS, a finding consistent with the effects of resolvinD1, a known antiinflammatory mediator.
authors.affiliation: 1 SCF Pharma, Ste-Luce, Quebec, Canada; and.|Departments of 2 Physiology and Biophysics, Faculty of Medicine and Health Sciences.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.affiliation: 3 Medicine, Respiratory Division, and.
authors.forename: André M
authors.initials: AM
authors.lastname: Cantin
authors.affiliation: Departments of 2 Physiology and Biophysics, Faculty of Medicine and Health Sciences.
authors.forename: Éric
authors.initials: É
authors.lastname: Rousseau
authors.affiliation: 4 Thoracic Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Sirois
authors.affiliation: 4 Thoracic Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Sirois
authors.affiliation: 3 Medicine, Respiratory Division, and.
authors.forename: Edmond
authors.initials: E
authors.lastname: Rizcallah
authors.affiliation: 1 SCF Pharma, Ste-Luce, Quebec, Canada; and.
authors.forename: Samuel
authors.initials: S
authors.lastname: Fortin
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000473:pathology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D050178:Monoglycerides / Q000494:pharmacology*; D055271:Mucin 5AC / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; C505032:CFTR protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; D050178:Monoglycerides; D055271:Mucin 5AC; D016328:NF-kappa B; C575982:docosahexaenoic acid monoacylglyceride; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: cystic fibrosis; cystic fibrosis transmembrane conductance regulator; docosahexaenoic acid; inflammation; lung