title: Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG-DHA in association with ASA in human bronchi.
abstract: The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 μM ASA (a COX inhibitor), the inhibitory effect of 1 μM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFα detection, hence preventing IκBα degradation and p65-NFκB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on β-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Rayan
authors.initials: R
authors.lastname: Khaddaj-Mallat
authors.affiliation: Service of Thoracic Surgery, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Sirois
authors.affiliation: Service of Thoracic Surgery, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Sirois
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Edmond
authors.initials: E
authors.lastname: Rizcallah
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. Electronic address: Eric.Rousseau@USherbrooke.ca.
authors.forename: Éric
authors.initials: É
authors.lastname: Rousseau
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001991:Bronchitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001993:Bronchodilator Agents / Q000819:agonists / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D050178:Monoglycerides / Q000819:agonists / Q000494:pharmacology*; D009124:Muscle Proteins; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D015525:Fatty Acids, Omega-3; C114479:GPR32 protein, human; C578095:IL13 protein, human; D018793:Interleukin-13; D047908:Intracellular Signaling Peptides and Proteins; D050178:Monoglycerides; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; C498143:RELA protein, human; D043562:Receptors, G-Protein-Coupled; C439524:TNF protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C575982:docosahexaenoic acid monoacylglyceride; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D051550:I-kappa B Kinase; C496565:IKBKE protein, human; D010749:Phosphoprotein Phosphatases; D001241:Aspirin
keywords: Aspirin; Human bronchi; IL-13; P-CPI-17; Resolvin D1