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 μmol/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 0.1 μmol/L MAG‐DPA did not significantly reduce inflammatory biomarkers, the higher concentrations of MAG‐DPA (0.3 and 1 μmol/L) blunted the activation of the TNF‐α/NF κB pathway and abolished COX‐2 expression in human and guinea pig tissues. Moreover, 0.3 and 1 μmol/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 1 μmol/L MAG‐DPA. This effect was further amplified in the presence of 100 μmol/L aspirin. MAG‐DPA mediates antiphlogistic effects by increasing the resolution of inflammation, while resetting Ca2+ sensitivity and contractile reactivity.

Highlights

  • Chronic asthma is distinguished from milder variants by increased airway inflammation and hyperresponsiveness (Murdoch and Lloyd 2010; Olin and Wechsler 2014)

  • concentration–response curves (CCRC) demonstrated that 48 h pretreatment with 10 ng/mL tumor necrosis factor alpha (TNF-a) induced a hyperresponsiveness to MCh with an apparent EC50 value and a mean maximal tension (MT, g) of 0.09 lmol/L and 1.15 Æ 0.07 g comparatively to 0.05 lmol/L and 0.23 Æ 0.05 g in control conditions

  • CCRC to histamine showed that 48 h pretreatment with 10 ng/mL TNF-a significantly increased the responsiveness to this agonist and reduced the apparent EC50 value and MT to 0.5 lmol/L and 1.2 Æ 0.07 g compared to control conditions (EC50 values of 1 lmol/L, MT of 0.40 Æ 0.01 g) (Fig. 1B)

Read more

Summary

Introduction

Chronic asthma is distinguished from milder variants by increased airway inflammation and hyperresponsiveness (Murdoch and Lloyd 2010; Olin and Wechsler 2014). NÀ3 PUFA levels are decreased in airway illnesses which are characterized by excess airway inflammation and enhanced n6-PUFA, including arachidonic acid derivatives, as in the case of asthma (Connor 2000). Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Objectives
Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.