-
TheScientificWorldJournal 2012Preclinical atherosclerosis represents a crucial period associated with several pathophysiological reactions in the vascular wall. Failure to diagnose preclinical... (Review)
Review
Preclinical atherosclerosis represents a crucial period associated with several pathophysiological reactions in the vascular wall. Failure to diagnose preclinical atherosclerosis at this stage misses a major opportunity to prevent the long-term consequences of this disease. Surrogate biological and structural vascular markers are available to determine the presence and the extension of preclinical vascular injury in the general population. Examples of surrogate markers are carotid intima media thickness and biomarkers including high-sensitivity C-reactive protein, cell adhesion molecules and matrix metalloproteinases, and leukotrienes. Recently, leukotrienes have been implicated as mediators, biomarkers, and possible therapeutic targets in the context of subclinical atherosclerosis. The aim of this short paper is to focus on the relation between preclinical atherosclerosis and leukotrienes, with particular attention to the recent development on the use of leukotriene modifiers in the treatment of atherosclerosis.
Topics: Animals; Arachidonate 5-Lipoxygenase; Atherosclerosis; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Disease Progression; Humans; Inflammation; Leukotrienes; Mice; Models, Biological; Placebos; Risk
PubMed: 22645425
DOI: 10.1100/2012/490968 -
Thorax Oct 2022Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory...
INTRODUCTION
Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis.
AIM
The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.
METHODS
Six healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF).
RESULTS
In the stable state, in serum there were significantly higher levels of prostaglandin E (PGE), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B (LTB) in patients with moderate-severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A (LXA) in severe bronchiectasis.In BALF, there were significantly higher levels of PGE, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB in moderate-severe patients compared with healthy volunteers.In the stable state, there was a negative correlation of PGE and LTB with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses.LXA improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA reduced neutrophil activation and degranulation.
CONCLUSION
There is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA in bronchiectasis warrants further studies.
Topics: Humans; Lipoxins; Prostaglandins; Bronchiectasis; Dinoprostone; Neutrophils; Anti-Inflammatory Agents; Leukotriene B4
PubMed: 34789559
DOI: 10.1136/thoraxjnl-2020-216475 -
TheScientificWorldJournal Jun 2002The leukotrienes are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4 is a classical chemoattractant, which triggers adherence and... (Review)
Review
The leukotrienes are a family of lipid mediators involved in inflammation and allergy. Leukotriene B4 is a classical chemoattractant, which triggers adherence and aggregation of leukocytes to the endothelium at only nM concentrations. In addition, leukotriene B4 modulates immune responses, participates in the host defense against infections, and is a key mediator of PAF-induced lethal shock. Because of these powerful biological effects, leukotriene B4 is implicated in a variety of acute and chronic inflammatory diseases, e.g., nephritis, arthritis, dermatitis, and chronic obstructive pulmonary disease. The final step in the biosynthesis of leukotriene B4 is catalyzed by leukotriene A4 hydrolase, a unique bifunctional zinc metalloenzyme with an anion-dependent aminopeptidase activity. Here we describe the most recent developments regarding our understanding of the function and molecular architecture of leukotriene A4 hydrolase.
Topics: Catalysis; Chemotactic Factors; Epoxide Hydrolases; Leukotrienes; Models, Molecular; Protein Structure, Quaternary; Structure-Activity Relationship
PubMed: 12806167
DOI: 10.1100/tsw.2002.810 -
Pharmacological Reports : PR 2010The metabolism of arachidonic acid into biologically active compounds involves the sequential activity of a number of enzymes, sometimes showing a unique expression... (Review)
Review
The metabolism of arachidonic acid into biologically active compounds involves the sequential activity of a number of enzymes, sometimes showing a unique expression profile in different cells. The main metabolic pathways, namely the cyclooxygenases and the 5-lipoxygenase, both generate chemically unstable intermediates: prostaglandin (PG) H(2) and leukotriene (LT) A(4), respectively. These are transformed by secondary enzymes into a variety of chemical structures known collectively as the lipid mediators. Although some cells express all the enzymes necessary for the production of biologically active compounds, it has been shown that eicosanoids are often the result of cell-cell interactions involving the transfer of biosynthetic intermediates, such as the chemically reactive PGH(2) and LTA(4), between cells. This process has been defined as the transcellular pathway of eicosanoid biosynthesis and requires both a donor cell to synthesize and release one component of the biosynthetic cascade and an accessory cell to take up that intermediate and process it into the final biologically active product. This review will summarize the evidence for transcellular biosynthetic events, occurring in isolated cell preparations, complex isolated organ systems, and in vivo, that result in the production of prostaglandins, leukotrienes, and lipoxins.
Topics: Animals; Arachidonic Acid; Cell Communication; Eicosanoids; Humans; Leukotriene A4; Leukotrienes; Metabolic Networks and Pathways; Models, Biological; Prostaglandin H2; Prostaglandins; Tissue Distribution
PubMed: 20631414
DOI: 10.1016/s1734-1140(10)70306-6 -
Respiratory Research Sep 2022Air pollutants can activate low-grade subclinical inflammation which further impairs respiratory health. We aimed to investigate the role of polygenic susceptibility to...
BACKGROUND
Air pollutants can activate low-grade subclinical inflammation which further impairs respiratory health. We aimed to investigate the role of polygenic susceptibility to chronic air pollution-induced subclinical airway inflammation.
METHODS
We used data from 296 women (69-79 years) enrolled in the population-based SALIA cohort (Study on the influence of Air pollution on Lung function, Inflammation and Aging). Biomarkers of airway inflammation were measured in induced-sputum samples at follow-up investigation in 2007-2010. Chronic air pollution exposures at residential addresses within 15 years prior to the biomarker assessments were used to estimate main environmental effects on subclinical airway inflammation. Furthermore, we calculated internally weighted polygenic risk scores based on genome-wide derived single nucleotide polymorphisms. Polygenic main and gene-environment interaction (GxE) effects were investigated by adjusted linear regression models.
RESULTS
Higher exposures to nitrogen dioxide (NO), nitrogen oxides (NO), particulate matter with aerodynamic diameters of ≤ 2.5 μm, ≤ 10 μm, and 2.5-10 µm significantly increased the levels of leukotriene (LT)B by 19.7% (p-value = 0.005), 20.9% (p = 0.002), 22.1% (p = 0.004), 17.4% (p = 0.004), and 23.4% (p = 0.001), respectively. We found significant effects of NO (25.9%, p = 0.008) and NO (25.9%, p-value = 0.004) on the total number of cells. No significant GxE effects were observed. The trends were mostly robust in sensitivity analyses.
CONCLUSIONS
While this study confirms that higher chronic exposures to air pollution increase the risk of subclinical airway inflammation in elderly women, we could not demonstrate a significant role of polygenic susceptibility on this pathway. Further studies are required to investigate the role of polygenic susceptibility.
Topics: Aged; Air Pollutants; Air Pollution; Biomarkers; Environmental Exposure; Female; Humans; Inflammation; Leukotrienes; Nitrogen Dioxide; Nitrogen Oxides; Particulate Matter
PubMed: 36151579
DOI: 10.1186/s12931-022-02179-3 -
Progress in Lipid Research Jan 2015Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of... (Review)
Review
Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of lipid peroxidizing enzymes and human lipoxygenase isoforms have been implicated in the pathogenesis of inflammatory, hyperproliferative (cancer) and neurodegenerative diseases. Lipoxygenases are not restricted to humans but also occur in a large number of pro- and eucaryotic organisms. Lipoxygenase-like sequences have been identified in the three domains of life (bacteria, archaea, eucarya) but because of lacking functional data the occurrence of catalytically active lipoxygenases in archaea still remains an open question. Although the physiological and/or pathophysiological functions of various lipoxygenase isoforms have been studied throughout the last three decades there is no unifying concept for the biological importance of these enzymes. In this review we are summarizing the current knowledge on the distribution of lipoxygenases in living single and multicellular organisms with particular emphasis to higher vertebrates and will also focus on the genetic diversity of enzymes and receptors involved in human leukotriene signaling.
Topics: Animals; Evolution, Molecular; Genetic Variation; Humans; Leukotrienes; Lipoxygenases; Phylogeny; Receptors, Leukotriene; Signal Transduction; Vertebrates
PubMed: 25435097
DOI: 10.1016/j.plipres.2014.11.001 -
FEBS Letters Jan 2001Leukotrienes are important lipid mediators implicated in the regulation of various cellular processes and in disease states as well as homeostasis. Regulation of... (Review)
Review
Leukotrienes are important lipid mediators implicated in the regulation of various cellular processes and in disease states as well as homeostasis. Regulation of leukotriene biosynthesis is therefore of considerable interest. Although the levels of expression and catalytic activity of leukotriene-forming proteins have long been recognized as important determinants of leukotriene biosynthesis, it has recently become apparent that their intracellular compartmentalization also affects the integrated output of this biosynthetic pathway. In this minireview, we focus on the unexpected discovery that the nucleus is the key intracellular site for leukotriene biosynthesis and discuss the mechanisms that regulate protein localization and the potential implications of these findings.
Topics: Animals; Arachidonate 5-Lipoxygenase; Cell Compartmentation; Cell Nucleus; Humans; Inflammation Mediators; Leukotrienes; Nuclear Envelope
PubMed: 11163352
DOI: 10.1016/s0014-5793(00)02374-7 -
Allergy Jan 2021Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological... (Review)
Review
Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological processes relevant to asthma, allergies, and allied diseases. Prostaglandins and leukotrienes are the most studied eicosanoids and established inducers of airway pathophysiology including bronchoconstriction and airway inflammation. Drugs inhibiting the synthesis of lipid mediators or their effects, such as leukotriene synthesis inhibitors, leukotriene receptors antagonists, and more recently prostaglandin D receptor antagonists, have been shown to modulate features of asthma and allergic diseases. This review, produced by an European Academy of Allergy and Clinical Immunology (EAACI) task force, highlights our current understanding of eicosanoid biology and its role in mediating human pathology, with a focus on new findings relevant for clinical practice, development of novel therapeutics, and future research opportunities.
Topics: Asthma; Consensus; Eicosanoids; Humans; Hypersensitivity; Leukotrienes
PubMed: 32279330
DOI: 10.1111/all.14295 -
Immunologic Research May 2014Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism and are markers and mediators of pulmonary... (Review)
Review
Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism and are markers and mediators of pulmonary inflammation. Research over the past two decades has established that LTs modulate inflammation in pulmonary arterial hypertension (PAH). The purpose of this review was to summarize the current knowledge of LTs in the pathophysiology of PAH and to highlight a recent study that advances our understanding of how leukotriene B4 (LTB4) specifically contributes to pulmonary vascular remodeling. The results of these studies suggest that pharmacological inhibition of LT pathways, especially LTB4, has high potential for the treatment of PAH.
Topics: Animals; Arachidonate 5-Lipoxygenase; Bone Morphogenetic Protein Receptors, Type II; Humans; Hypertension, Pulmonary; Leukotrienes; Pulmonary Artery; Signal Transduction
PubMed: 24570092
DOI: 10.1007/s12026-014-8492-5 -
The Western Journal of Medicine Oct 1985Although prostaglandin research began about 50 years ago, many of the most important advances in understanding the biochemistry, physiology and pharmacology have taken... (Review)
Review
Although prostaglandin research began about 50 years ago, many of the most important advances in understanding the biochemistry, physiology and pharmacology have taken place within the past five to ten years. There is great potential for the extension of this research to the clinical practice of medicine. At this time, the most common interaction that clinicians have with the prostaglandin field is in administering nonsteroidal anti-inflammatory drugs, which function by inhibiting prostaglandins. The uses of these drugs include treating not only inflammation, but also dysmenorrhea, some renal disease, thrombotic diseases and some metabolic disorders. Prostaglandin analogs, with their potent effects on uterine contraction, are in common use in obstetrics. Other analogs, with gastric and duodenal cytoprotective effects are useful in treating peptic ulcer disease. Future benefits from prostaglandin and leukotriene research may include new therapy for inflammatory and hypersensitivity diseases such as asthma, inflammatory bowel diseases and dermatitis.
Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Diseases; Chemical Phenomena; Chemistry; Digestive System; Digestive System Physiological Phenomena; Female; Humans; Immunity, Cellular; Inflammation; Kidney; Leukotriene B4; Lung; Lung Diseases; Male; Metabolic Diseases; Pregnancy; Prostaglandin Antagonists; Prostaglandins; Reproduction; SRS-A; Thromboxanes; Uterine Contraction
PubMed: 3004043
DOI: No ID Found