Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi

Tabet, Yacine; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric

doi:10.1152/ajplung.00379.2012

Cited by 7 publications

(4 citation statements)

References 36 publications

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“…In addition, in the human bronchus experiments, several products of CYP activity, such as the arachidonic (EpETrEs) and linoleic acid epoxides (EpOMEs), were significantly decreased by ∼80% following FLAP/5-LOX inhibition (Figure 3). Compounds from these two classes have been reported to exert anti-inflammatory properties in human bronchus 19 and represent a potential therapeutic target for inflammatory lung disease. 20,21 Changes in EpETrEs and EpOMEs by inhibition of FLAP/5-LOX have not been reported previously and should be further investigated using the human bronchus preparation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Lipid Mediator Quantification in Isolated Human and Guinea Pig Airways: An Expanded Approach for Respiratory Research

et al. 2018

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The clinical importance of prostaglandins and leukotrienes in asthma is well recognized; however, the biochemical role of other lipid mediators (often termed oxylipins) in the regulation of airway tone and inflammation remains unclear. We therefore developed a workflow to investigate oxylipin physiology and pharmacology in two in vitro models, the intact human bronchus and the guinea pig trachea. Airways were isolated and smooth muscle contraction was measured in an organ bath following stimulation with either anti-IgE or ovalbumin. The associated release of oxylipins over time into the organ bath was quantified using three developed LC-MS/MS methods capable of collectively measuring 130 compounds. Oxylipin extraction recoveries were 71% on average, method accuracy was 90-98%, coefficient of variation was 4.3-9.4%, and matrix effects were on average 11%. At baseline, low levels of primarily prostaglandins and associated metabolites were observed in both tissue preparations. The mast cell-induced airway constriction caused release of leukotrienes and further elevations in prostaglandin levels. In total, 57 oxylipins from the human bronchus, and 42 from guinea pig trachea, were detected at 60 min post-stimulation in the organ bath. Chiral analysis demonstrated that 5-hydroxyeicosatetraenoic acid (5-HETE) in the human bronchus preparation was not produced by 5-LOX enzymatic activity (enantiomeric excess [ee] = 10%), as opposed to 12( S)-HETE, 14( S)-, and 17( S)-hydroxy docosahexaenoic acid (HDoHE; ee = 100%), highlighting that chiral chromatography is necessary for correct biological interpretation. Unexpectedly, prostaglandin D and its metabolites remained elevated 24 h after the challenges, suggesting a sustained activation of mast cells not previously described. The reported translational methodology provides a new platform for comprehensive studies to elucidate the origin and functions of individual oxylipins in various airway responses.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Lipid Mediator Quantification in Isolated Human and Guinea Pig Airways: An Expanded Approach for Respiratory Research

et al. 2018

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“…hyperpolarization in human bronchi and the synthesis of the bronchorelaxing/hyperpolarizing factors epoxyeicosatrienoic acids produced by the endogenous CYP450 epoxygenase indicating a role for these arachidonic acid metabolites in hyperpolarization, via the large conductance Ca 2+sensitive K + channel, of airway smooth muscle cells induced by bradykinin (Tabet et al, 2013).…”

Section: Tabet Et Al Demonstrated a Relationship Between Bradykinin-mentioning

confidence: 99%

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Ricciardolo

Folkerts

Folino

et al. 2018

European Journal of Pharmacology

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Bradykinin, a pro-inflammatory molecule, and its related peptides have been studied for their effects on acute reactions in upper and lower airways, where they can be synthesised and metabolized after exposure to different stimuli including allergens and viral infection. Bradykinin B and B receptors are constitutively expressed in the airways on several residential and/or immune cells. Their expression can also be induced by inflammatory mediators, usually associated with eosinophil and neutrophil recruitment, such as IL-4, IL-13, TNF-α, IL-6 and IL-8, via intracellular MAPK and NF-κB signalling. In turn, the latters up-regulate both bradykinin receptors. Bradykinin activates epithelial/endothelial and immune cells, neurons and mesenchymal cells (such as fibroblasts, myofibroblasts and smooth muscle cells), which are implicated in the development of airway chronic inflammation, responsiveness and remodelling (a major feature of severe asthma). This review highlights the role of bradykinin and its receptors in respect to chronic inflammatory response involving eosinophils/neutrophils and to vascular/matrix-related airway remodelling in asthmatic airways. This scenario is especially important for understanding the mechanisms involved in the pathogenesis of eosinophilic and/or neutrophilic asthma and hence their therapeutic approach.

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“…Nonetheless, TP may play other roles in smooth muscle in terms of actin polymerization (and thus tissue stiffening) (156,157). Furthermore, interactions of TP with other GPCRs could be relevant to understanding whether specific constricting (263,310) or dilating agents (420,476,510) (such as BTRs) may be more potent under certain conditions.…”

Section: L1117 Smooth Muscle and Beyondmentioning

confidence: 99%

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

Prakash

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

114

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Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease.

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Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi

Cited by 7 publications

References 36 publications

Lipid Mediator Quantification in Isolated Human and Guinea Pig Airways: An Expanded Approach for Respiratory Research

Lipid Mediator Quantification in Isolated Human and Guinea Pig Airways: An Expanded Approach for Respiratory Research

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

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