Lipoxin A<sub>4</sub> levels in asthma: relation with disease severity and aspirin sensitivity

Celik, GE; Fo, Erkekol; Mısırlıgil, Zeynep; Melli, Mehmet

doi:10.1111/j.1365-2222.2007.02806.x

Cited by 52 publications

(40 citation statements)

References 42 publications

(65 reference statements)

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“…Lipoxins are also formed in vivo and are associated with inflammatory events, as LXA 4 is present in BALF from patients with respiratory inflammation (29). Individuals with asthma possess the capacity to generate LXs, but activated whole blood from aspirin-intolerant subjects with asthma and subjects with severe asthma displays relative decrements in LXA 4 biosynthesis (24,30,31). In contrast to LXs, leukotriene levels (LTB 4 and CysLTs) are increased in activated whole blood from subjects with severe asthma compared with those with nonsevere asthma (24).…”

Section: Discussionmentioning

confidence: 99%

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma

Planagumà

Kazani

Marigowda

et al. 2008

Am J Respir Crit Care Med

216

194

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Rationale: Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A 4 (LXA 4 ) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation. Objectives: Airway levels of LXA 4 , as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma. Methods: Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA 4 and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA 4 receptors were monitored by flow cytometry. Measurements and Main Results: Individuals with severe asthma had significantly less LXA 4 in bronchoalveolar lavage fluids (11.2 6 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 6 38.5 pg/ml; P , 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA 4 receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes. Conclusions: Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.

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Section: Discussionmentioning

confidence: 99%

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma

Planagumà

Kazani

Marigowda

et al. 2008

Am J Respir Crit Care Med

216

194

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“…Leukotriene receptor antagonists are widely used as another first-line therapeutic agent in asthma, suggesting that abnormal lipid metabolism contributes to disease pathophysiology. Recently, several reports have indicated that biosynthesis of anti-inflammatory and pro-resolving lipid mediators, lipoxin A4 (LXA4) or protectin D1 (PD1), are dysregulated in severe asthma (12)(13)(14)(15)(16)(17)(18)(19)(20)(21), suggesting that an imbalance between pro-and anti-inflammatory molecules causes the exacerbation of inflammation observed in airways of asthmatic patients.…”

Section: Introductionmentioning

confidence: 99%

Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases

Miyata

Arita

2015

Allergology International

183

144

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Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found naturally in fish oil and are commonly thought to be anti-inflammatory nutrients, with protective effects in inflammatory diseases including asthma and allergies. The mechanisms of these effects remain mostly unknown but are of great interest for their potential therapeutic applications. Large numbers of epidemiological and observational studies investigating the effect of fish intake or omega-3 fatty acid supplementation during pregnancy, lactation, infancy, childhood, and adulthood on asthmatic and allergic outcomes have been conducted. They mostly indicate protective effects and suggest a causal relationship between decreased intake of fish oil in modernized diets and an increasing number of individuals with asthma or other allergic diseases. Specialized pro-resolving mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3 fatty acids such as EPA and DHA via several enzymatic reactions. These mediators counter-regulate airway eosinophilic inflammation and promote the resolution of inflammation in vivo. Several reports have indicated that the biosynthesis of SPM is impaired, especially in severe asthma, which suggests that chronic inflammation in the lung might result from a resolution defect. This article focuses on the beneficial aspects of omega-3 fatty acids and offers recent insights into their bioactive metabolites including resolvins and protectins.

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“…LXs play a key counterregulatory role in mouse models of infection with Mycobacterium tuberculosis and Toxoplasma gondii ( 1 -3, 7 ). Similarly, defi cient LX-mediated counterregulation has been linked to the pathogenesis of infl ammatory diseases, such as severe asthma ( 8 ), cystic fi brosis lung disease ( 3 ), and periodontal disease ( 7 ). The benefi cial eff ects of LX analogue administration in diverse rodent models of infl ammatory pathology, along with the observation that administration of the widely used antiinfl ammatory drug ASA leads to the generation of metabolically more stable LX carbon 15-epimers (ASA-triggered LX [ATL]), has suggested therapeutic promise for specifi c harnessing of the biological activities of these potent lipid mediators.…”

mentioning

confidence: 99%

Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

Machado¹,

Esper²,

Dias³

et al. 2008

J Cell Biol

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Lipoxin A₄ levels in asthma: relation with disease severity and aspirin sensitivity

Abstract: This study indicated that diminished LX A4 generation was unique to severe asthma phenotype regardless of comorbid aspirin sensitivity. Clinical Implications Lower LX A4 levels in severe asthma would suggest a possibility for LX analogues as future treatment options in these patients.

Cited by 52 publications

References 42 publications

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma

Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases

Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

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Lipoxin A4 levels in asthma: relation with disease severity and aspirin sensitivity

Abstract: This study indicated that diminished LX A4 generation was unique to severe asthma phenotype regardless of comorbid aspirin sensitivity. Clinical Implications Lower LX A4 levels in severe asthma would suggest a possibility for LX analogues as future treatment options in these patients.

Cited by 52 publications

References 42 publications

Airway Lipoxin A4Generation and Lipoxin A4Receptor Expression Are Decreased in Severe Asthma

Airway Lipoxin A4Generation and Lipoxin A4Receptor Expression Are Decreased in Severe Asthma

Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases

Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

Contact Info

Product

Resources

About

Lipoxin A₄ levels in asthma: relation with disease severity and aspirin sensitivity

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma

Airway Lipoxin A₄Generation and Lipoxin A₄Receptor Expression Are Decreased in Severe Asthma