Open AccessMAG ‐ DPA curbs inflammatory biomarkers and pharmacological reactivity in cytokine‐triggered hyperresponsive airway models
Author(s) -
KhaddajMallat Rayan,
Hiram Roddy,
Sirois Chantal,
Sirois Marco,
Rizcallah Edmond,
Marouan Sofia,
Morin Caroline,
Rousseau Éric
Publication year - 2016
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.263
Subject(s) - guinea pig , western blot , chemistry , inflammation , cytokine , pharmacology , microbiology and biotechnology , medicine , immunology , biology , biochemistry , gene
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 ‐ α 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 μ mol/L). Pharmacomechanical reactivity, Ca 2+ 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 μ mol/L MAG ‐ DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG ‐ DPA (0.3 and 1 μ mol/L) blunted the activation of the TNF ‐ α / NF κ B pathway and abolished COX ‐2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 μ mol/L MAG ‐ DPA consistently decreased the Ca 2+ sensitivity and pharmacological reactivity of cultured bronchial explants. Furthermore, in human bronchi, IL ‐13‐stimulated phosphorylation of CPI ‐17 was reversed by 1 μ mol/L MAG ‐ DPA . This effect was further amplified in the presence of 100 μ mol/L aspirin. MAG ‐ DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca 2+ sensitivity and contractile reactivity.