Untapped Potential: Therapeutically Targeting Eicosanoids and Endocannabinoids in the Lung

Yonker, Lael M.; Barrios, Juliana; Mou, Hongmei; Hurley, Bryan P.

doi:10.1002/cpt.2165

Cited by 8 publications

(10 citation statements)

References 113 publications

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“…44 sPLA2 has been reported to have involved in neutrophilic asthma as well as severe asthma. 45,46 The activation of iPLA2 promotes macrophage polarization towards the M1 inflammatory phenotype. 47 Neutrophil-induced reactive oxygen species is mediated by iPLA2 among patient with metabolic dysregulation.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulated surfactant protein B in obese asthmatics

Cao

Moon

Yoo

et al. 2022

Clin Experimental Allergy

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Background: Obesity is a common comorbid condition in adult asthmatics and known as a feature of asthma severity. However, the molecular mechanism under obesityinduced inflammation has not yet been fully understood.Objective: Considering the essential role of hydrophobic surfactant protein B (SP-B) in lung function, SP-B was targeted to examine its involvement in the development of obesity-induced airway inflammation in asthmatics. Methods:The aim was to examine an alteration in circulating SP-B according to obesity in adult asthmatics, 129 asthmatics were enrolled and classified into 3 groups (obese, overweight and normal-weight groups) according to body mass index (BMI).Circulating SP-B levels were determined by enzyme-linked immunosorbent assay.Four single nucleotide polymorphisms of SFTPB gene were genotyped. Serum ceramide levels were measured by liquid chromatography-tandem mass spectrometry.Results: Significantly lower serum SP-B levels were noted in the obese group than in the overweight or normal-weight group (p = .002). The serum SP-B level was significantly correlated with serum levels of C18:0 ceramide and transforming growth factor beta 1 as well as BMI (r = −0.200; r = −0.215; r = −0.332, p < .050 for all). An inverse correlation was noted between serum SP-B and fractional exhaled nitric oxide levels in female asthmatics (r = −0.287, p = .009). Genetic predisposition of the SFTPB gene at 9306 A>G to the obese and overweight groups was noted. Conclusion:Obesity altered ceramide metabolism leading to pulmonary surfactant dysfunction and impaired resolution of airway inflammation, finally contributing to the phenotypes of obese asthmatics.

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Section: Discussionmentioning

confidence: 99%

Down‐regulated surfactant protein B in obese asthmatics

Cao

Moon

Yoo

et al. 2022

Clin Experimental Allergy

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“…LMs are a large class of biologically active substances derived from the oxidation and metabolism of 20-carbon polyunsaturated fatty acids in the body, such as prostaglandins, hydroxy eicosatetraenoic acid (HETE), leukotrienes, epoxy fatty acids (EET), and thromboxanes (TXs) (Sheppe and Edelmann, 2021). Several lipid mediators are involved in the process of inflammation, and they develop a complete metabolic network during immune and structural cell metabolism and signalling (Sokolowska et al, 2021;Yonker et al, 2021). Moreover, it has also been demonstrated that there is a close relationship between disorders arising from the metabolism of LMs and the development and progression of asthma, manifested as lesions of the respiratory airway, blood vessels, and lung parenchyma (Su et al, 2018;Barden et al, 2021).…”

Section: Graphical Abstract 1 Introductionmentioning

confidence: 99%

The influence of Hyssopus cuspidatus Boriss extract on lipid mediators metabolism network in asthmatic mice

Kong

Xiao-Juan²,

Yan³

et al. 2023

Front. Pharmacol.

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Current drugs do not provide an absolute cure or modify the course of asthma. Hyssopus cuspidatus Boriss extract (SXCF) has been used as Uyghur medicine for several years to treat bronchial asthma. However, very limited research has been conducted on the therapeutic mechanisms of SXCF. Disruptions in the metabolic network of lipid mediators (LMs) are closely linked to the development of asthma. Here, we explored the therapeutic mechanism of SXCF in asthma based on the metabolic network of LMs, aiming to contribute to the understanding of SXCF in asthma treatment at the molecular level. The UHPLC-MRM strategy was used for the quantitative detection of LMs in the lung tissue and in the peripheral circulatory system (serum). ELISA was used to detect IgE in serum and cytokines in BALF. The lung tissue sections were stained with H&E to observe the infiltration of inflammatory cells, and behavioural changes in mice were observed and recorded throughout the animal experiment. In contrast to the asthma group, the opposite result was observed in the SXCF groups, where the perturbed LMs metabolic network was partly restored in a dose-dependent manner with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. As significant downregulation of IgE and pro-inflammatory cytokines was observed, IgE and cytokines analysis also supported the anti-inflammatory effects of SXCF. It was also noticed that SXCF treatment reduced the number of coughs and decreased the inflammatory cell infiltration around the bronchus in mice. These results suggested that SXCF has a significant ameliorative effect on ovalbumin (OVA)-induced asthma. The modulation of LMs is a possible underlying mechanism of the SXCF effects.

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“…The resolution of acute inflammation consists in switching the synthesis of proinflammatory lipid mediators to the formation of SPMs [28]. The impairment of this process underlies the development of chronic inflammation [29,30,31,32,33]. Therefore, the study of the role of eicosanoids, SPM and endocannabinoids in the regulation of inflammatory responses in bronchial asthma allows us to expand our understanding of the mechanisms of impaired resolution of inflammation and find new targets for asthma treatment.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2023

Russ Open Med J

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Asthma is a common chronic heterogeneous inflammatory respiratory disease with complex pathogenesis. Chronic lung inflammation can be the result of a defect in the resolution of the inflammatory process caused by an imbalance between the synthesis of proinflammatory and pro-resolving lipid mediators. The identification of immunomodulatory effects of eicosanoids, specialized proresolving mediators (SPMs), and endocannabinoids synthesized from polyunsaturated fatty acids (PUFAs) allows taking a fresh look at the ways of controlling inflammation rather than solely at its mechanisms. The use of ω-3 PUFA-containing food supplements in combination with standard therapy leads to improved asthma control due to the ability of ω-3 PUFAs to stimulate SPM synthesis and inhibit intracellular signaling pathways of inflammation. Lipid mediators are agonists of peroxisome proliferator-activated receptors (PPARs) and glucocorticoid receptors (GR) that have anti-inflammatory properties. The receptors that are widely expressed in the pulmonary epithelium, endothelium, dendritic cells, eosinophils, fibroblasts, and macrophages play an important role in the regulation of immunometabolic homeostasis in the bronchopulmonary system. Our review systematizes the published data on the properties and mechanism of action of biologically active ω-3 and ω-6 PUFAs involved in the inflammatory process in asthma. Also, this article presents the prospects of using ω-3 PUFAs for the resolution of inflammation in asthma.

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Untapped Potential: Therapeutically Targeting Eicosanoids and Endocannabinoids in the Lung

Cited by 8 publications

References 113 publications

Down‐regulated surfactant protein B in obese asthmatics

Down‐regulated surfactant protein B in obese asthmatics

The influence of Hyssopus cuspidatus Boriss extract on lipid mediators metabolism network in asthmatic mice

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