An update on the role of leukotrienes in asthma

Abstract

Purpose of review-Leukotrienes (LT)s are lipid mediators involved in the pathogenesis of asthma. There is significant new information about the actions of LTs in asthma, and the evolving role of anti-LT therapies. We review recent findings on regulation of LT synthesis, biological function of LTs in disease models, and use of LT modifiers in clinical practice.Recent findings-Our understanding of the regulation of LT synthesis at a molecular level has greatly advanced. Recent evidence indicates that genetic variation in the leukotriene synthetic pathway affects the clinical response to LT modifiers. The participation of LTB 4 in the allergic sensitization process in animal models suggests a larger role for LTB 4 in asthma. Preclinical and in vitro models suggest that the cysteinyl LT (CysLT)s are important in airway remodeling. LTs are key mediators of exercise-induced bronchoconstriction (EIB) with recent studies demonstrating that LT modifiers reduce the severity of EIB during short-term and long-term use.Summary-LTs are clearly involved in airway inflammation and certain clinical features of asthma. Evolving evidence indicates that LTB 4 has an important role in the development of asthma, and that CysLTs are key mediators of the airway remodeling process.

Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation

“…Sodium [ 125 I] iodine (carrier-free, 3.7 GBq/ml) was purchased from Perkin Elmer (Boston, MA). ELISA kits for determination of IL-4 and IL-5 levels were obtained from R&D systems; the ELISA kit for IFN-g was obtained from Raybiotech (Norcross, GA); the ELISA kits for LTB 4 , cysteinyl leukotrienes (CysLTs), PGD 2 , and PGE 2 were obtained from Cayman Chemical (Ann Arbor, MI); the ELISA kit for 15-deoxy-D 12,14 -PGJ 2 (15d-PGJ 2 ) was obtained from Enzo Life Science (Farmingdale, NY); and ELISA kits for sPLA 2 -IB and sPLA 2 -X were obtained from Cusabio Biotech (Wuhan, China). Cell culture reagents were obtained from Sigma-Aldrich (Tokyo, Japan) and Invitrogen (Carlsbad, CA).…”

“…t has been shown that eicosanoids, including leukotrienes (LT) and PGs, have crucial roles in the pathogenesis of airway inflammation (1)(2)(3)(4). These eicosanoids are 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acids, and the cellular availability of arachidonic acid is tightly controlled by hydrolysis of membrane phospholipids via the catalytic activity of phospholipases A 2 (PLA 2 ) (5-10).…”

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

“…Установлено, что инфильтрация респираторного тракта дыхательных путей эозинофилами и последующая их дегрануляция сопровождаются высвобождением цито-токсических продуктов (эозинофильные катионные бел-ки, нейротоксины, пероксидазы), которые вносят зна-чительный вклад в повреждение эпителия дыхательных путей, гиперпродукцию слизи бокаловидными клетками, бронхиальную гиперреактивность и нарушение функ-ции мерцательного эпителия. Эозинофилы секретируют цистеиниловые лейкотриены (Cysteinyl leukotrienes, LTC4, LTD4 и LТЕ4), которые являются мощными провоспали-тельными медиаторами и вызывают бронхоспазм, повы-шение проницаемости сосудов, гиперсекрецию слизи и активацию эозинофилов [11,12]. Кроме того, эозино-филы синтезируют факторы роста, такие как трансформи-рующий фактор роста (Transforming growth factor, TGF) ␤, тем самым участвуют в развитии таких структурных изме-нений дыхательных путей, как утолщение эпителиаль-ной базальной мембраны и гипертрофия гладких мышц [13].…”

n-3 Polyunsaturated fatty acids and mast cell activation

“…CysLTs have a strong effect on smooth muscle contraction and increased vascular permeability compared with 5-series LTs [191]. CysLTs can also induce eosinophil migration [192] and activate eosinophils and mast cells to secrete cytokines [193]. One-series PGs are anti-inflammatory; however, the level of DGLA in the body is low compared with that of EPA and AA [194].…”