title: MAG-DPA curbs inflammatory biomarkers and pharmacological reactivity in cytokine-triggered hyperresponsive airway models.
abstract: Bronchial inflammation contributes to a sustained elevation of airway hyperresponsiveness (AHR) in asthma. Conversely, omega-3 fatty acid derivatives have been shown to resolve inflammation in various tissues. Thus, the effects of docosapentaenoic acid monoacylglyceride (MAG-DPA) were assessed on inflammatory markers and reactivity of human distal bronchi as well as in a cultured model of guinea pig tracheal rings. Human bronchi were dissected and cultured for 48 h with 10 ng/mL TNF-αor IL-13. Guinea pig tracheas were maintained in organ culture for 72 h which was previously shown to trigger spontaneous AHR. All tissues were treated with increasing concentrations of MAG-DPA (0.1, 0.3, and 1μmol/L). Pharmacomechanical reactivity, Ca2+sensitivity, and western blot analysis for specific phosphoproteins and transcription factors were performed to assess the effects of both cytokines, alone or in combination with MAG-DPA, on human and guinea pig airway preparations. Although 0.1μmol/L MAG-DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG-DPA (0.3 and 1μmol/L) blunted the activation of the TNF-α/NFκB pathway and abolished COX-2 expression in human and guinea pig tissues. Moreover, 0.3 and 1μmol/L MAG-DPA consistently decreased the Ca2+sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL-13-stimulated phosphorylation of CPI-17 was reversed by 1μmol/L MAG-DPA. This effect was further amplified in the presence of 100μmol/L aspirin. MAG-DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca2+sensitivity and contractile reactivity.
authors.affiliation: Faculty of Medicine and Health Sciences Department of Obstetrics-Gynecology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Rayan
authors.initials: R
authors.lastname: Khaddaj-Mallat
authors.affiliation: Faculty of Medicine and Health Sciences Department of Obstetrics-Gynecology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Roddy
authors.initials: R
authors.lastname: Hiram
authors.affiliation: Faculty of Medicine and Health Sciences Service of Thoracic Surgery Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Sirois
authors.affiliation: Faculty of Medicine and Health Sciences Service of Thoracic Surgery Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Sirois
authors.affiliation: Faculty of Medicine and Health Sciences Department of Pathology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Edmond
authors.initials: E
authors.lastname: Rizcallah
authors.affiliation: Faculty of Medicine and Health Sciences Department of Pathology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Marouan
authors.affiliation: Faculty of Medicine and Health Sciences Department of Obstetrics-Gynecology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.affiliation: Faculty of Medicine and Health Sciences Department of Obstetrics-Gynecology Université de Sherbrooke Sherbrooke QC J1H 5N4 Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Rousseau
keywords: Airway hyperresponsiveness; docosapentaenoic acid; human bronchi; monoacylglyceride; resolution of inflammation