MAG-DPA curbs inflammatory biomarkers and pharmacological reactivity in cytokine-triggered hyperresponsive airway models.
Journal:
Pharmacology research & perspectives
Published Date:
Oct 18, 2016
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- or 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 1 mol/L). Pharmacomechanical reactivity, Ca 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 0.1 mol/L MAG-DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG-DPA (0.3 and 1 mol/L) blunted the activation of the TNF-/NF B pathway and abolished COX-2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 mol/L MAG-DPA consistently decreased the Ca sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL-13-stimulated phosphorylation of CPI-17 was reversed by 1 mol/L MAG-DPA. This effect was further amplified in the presence of 100 mol/L aspirin. MAG-DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca sensitivity and contractile reactivity.
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