The role of the mast cell in asthma. Response to A. M. Edwards by C. Brightling, P. Bradding

Brightling, Christopher; Bradding, Peter

doi:10.1046/j.1365-2222.2003.01740.x

Cited by 1 publication

(1 citation statement)

References 2 publications

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“…Furthermore, the amplitudes of pharmacological responses to various spasmogens confirmed the key role of proinflammatory cytokines in ASM hyperresponsiveness (Tliba et al 2003;Morin and Rousseau 2006). For instance, TNF-a is released from airway resident macrophages (Brightling et al 2008), whereas IL-13 is secreted by Th 2 cell-type responses (Tliba et al 2003). These proinflammatory cytokines also exert important amplifying effects on inflammatory biomarkers, which were reversed in a concentration-dependent manner by MAG-DPA in both mammalian models used in this study.…”

Section: Discussionsupporting

confidence: 70%

MAG ‐ DPA curbs inflammatory biomarkers and pharmacological reactivity in cytokine‐triggered hyperresponsive airway models

Khaddaj‐Mallat

Hiram

Sirois

et al. 2016

Pharmacol Res Perspect

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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.

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