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Asthma is a common allergic pathology of the respiratory tract that requires the study of mechanisms underlying it, due to severe forms of the disease, which are refractory to therapy. The review is devoted to the search for molecular targets of fatty acid ethanolamides in asthma, in particular palmitoylethanolamide (PEA), which has been successful...
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Context 1
... (N-palmitoylethanolamine, or PEA) was discovered in the late 1950s. It is an endogenous lipid mediator belonging to the class of fatty acid ethanolamides [38], acts as a signal compound, and is synthesized on demand from membrane phospholipids Figure 1. In addition, PEA is a natural lipid component found in nutritional products and food additives. ...
Citations
... Хотя БА имеет значительные генетический и экологический компоненты, эпидемиологические исследования свидетельствуют о взаимосвязи развития БА и нарушения питания [41,104,105]. Несмотря на то что вопрос о роли REVIEW НАУЧНЫЙ ОБЗОР микробиома в развитии БА остается открытым, клинические стратегии, направленные на модуляцию микробиома кишечника диетами, пробиотиками и пребиотиками, при различной патологии бронхолегочной системы уже были предприняты [106][107][108] и признаны многообещающим направлением в лечении заболеваний дыхательных путей [92]. Интересны данные исследования X.L. Zou et al. о связях между кишечной микробиотой и фенотипическими особенностями БА [110]. ...
Asthma is a chronic, heterogeneous inflammatory disease with a high variability of the flow caused by the trigger influence of genetic and environmental factors. The heterogeneity of asthma indicates the involvement of many components in the mechanism of the inflammation of the respiratory tract. Currently, the microbiotic concept of the pathogenesis of respiratory system diseases is studied, based on the existence of a bilateral relationship between the microflora lungs and the intestines. The key mechanism of these relationships is free fatty acids performing signal and regulatory functions in the body. The medium-chain and long-chain free fatty acids are synthesized by de novo or enter the body as a result of consumption of fats, while the short-chain free fatty acids are formed in the intestine as a result of partial digestion of soluble fibre. The mechanism connecting the free fatty acids and inflammatory reactions includes activation of their receptors (Free Fatty Acid Receptor, FFAR) expressed on the cells of the gastrointestinal and respiratory tract, as well as on immune cells. If the role of the medium-chain and long-chain fatty acids receptors (FFAR1, FFAR4) and their ligands in the pathogenesis of asthma is actively studied, the value of the short-chain receptors (FFAR2, FFAR3) only begins to attract the attention of researchers in connection with the emergence of numerous data on the interconnection of the respiratory microbiome paths and intestines and its possible role in the induction of broncho-pulmonary complications. This review includes modern knowledge of the microbiotic concept of asthma, the basic information about the nomenclature, metabolism and transport of the free fatty acids, the value of the individual classes of the free fatty acids in the regulation of immune processes is normal and at bronchopulmonary pathology. The latest data of the FFAR receptors are systematized, features of their activation and expression, the intended role of FFAR2 and FFAR3 in the development and asthma therapy. It is discussed that gastrointestinal microbiota correction can reduce the activity of chronic inflammation of the respiratory tract at asthma.
... Two major types of MCs have been detected and are distinguished by the content of their secretory granules [21]. MCs cells contain mainly tryptase as well as chymase and carboxypeptidase [22]. ...
Everyone wishes to appear younger. Actually, women spend a lot of efforts and money to fight aging appearance of skin. In the recent decade, skin aging has become an annoying social and medical problem at the levels of modern societies. Unfortunately, up to now, scientists have not discovered an effective treatment to overcome the appearance of the elderly skin. Although, researchers try hard to discover the main causes and mechanisms of getting skin more aged to earn a youthful look for skin appearance, some researchers suggested that mast cells (MCSs) were scarcely found neither in fetus dermis nor the youth while they are clearly detected in dermis of senile people which proposes the function of these cells in controlling the process of skin caducity. Researchers have taken into consideration the beneficial effect of MCS in controlling skin caducity. Recently, MCS is considered as an effective route in treatment elderly skin. Non-synthetic products can inhibit MCS activation so considered as a good functional ingredient fighting skin aging process as this cell implicated in skin damage and aging; degranulation of papillary dermal MCS might result in inflammation, reconstruction of extracellular matrix and angiogenesis with subsequently induced skin caducity. This mini review summarizes the crucial role of activated MCS in the dermal aging process. Keywords: skin; aging; mast cell.
... Plasmalogens are another important component of metabolic syndrome development since they contribute to cell membrane physiology and anatomy. Besides, plasmalogen are reservoirs of secondary messages and mediators of membrane dynamics and involved in membrane fusion, endogenous antioxidants, protecting lipids and lipoproteins from oxidative stress, neuroprotectors, modulators of the signaling mechanisms of cell membranes, transmembrane transport of fatty acids, ion transport, cholesterol efflux, membrane-bound enzyme activity, and diffusion of signal-transduction molecules [18][19][20][21][22]. The reduction of plasmalogen ethanolamine isotype associated with metabolic disorders, cardiovascular disease, Alzheimer's disease, Down syndrome, molecular signaling abnormalities, and tumors [22,23]. ...
Undeniably, lipid plays an extremely important role in the homeostasis balance, since lipid contributes to the regulation of the metabolic processes. The metabolic syndrome pathogenesis is multi-pathway that composes neurohormonal disorders, endothelial cell dysfunction, metabolic disturbance, genetic predisposition, in addition to gut commensal microbiota. The heterogenicity of the possible mechanisms gives the metabolic syndrome its complexity and limitation of therapeutic accesses. The main pathological link that lipid contributes to the emergence of metabolic syndrome via central obesity and visceral obesity that consequently lead to oxidative stress and chronic inflammatory response promotion. Physiologically, a balance is kept between the adiponectin and adipokines level to maintain the lipid level in the organism. Clinically, extremely important to define the borders of the lipid level in which the pathogenesis of the metabolic syndrome is reversible, otherwise will be accompanied by irreversible complications and sequelae of the metabolic syndrome (cardiovascular, insulin resistance). The present paper is dedicated to providing novel insights into the role of lipid in the development of metabolic syndrome hence dyslipidemia is the initiator of insulin resistance syndrome (metabolic syndrome).
... Широкая распространенность и трудность контроля течения хронических воспалительных заболеваний дыхательных путей, включая бронхиальную астму (БА) и хроническую обструктивную болезнь легких (ХОБЛ), указывает на необходимость выявления новых терапевтических мишеней [1,2]. В последние годы наблюдается интерес к изучению не только нейроиммунных механизмов хронизации воспаления в бронхолегочной системе [3,4], но и метаболических изменений, обусловленных нарушениями состава жирных кислот (ЖК) мембран клеток и синтеза липидных медиаторов, участвующих в разрешении острого воспаления [5][6][7]. Дисбаланс иммунной и метаболической систем имеет тесную двустороннюю взаимосвязь [8]. Например, метаболизм липидов регулирует дифференцировку CD4+ Т-клеток в направлении Т-эффекторных или Т-регуляторных клеток, которые играют важную роль в адаптивной иммунной системе и участвуют в патогенезе многих хронических воспалительных заболеваний. ...
Chronic inflammatory diseases of the respiratory tract, including asthma and chronic obstructive pulmonary disease, are a global problem of our time due to the widespread prevalence and difficulty of controlling the course. The mechanism of chronic inflammation in the bronchopulmonary system is closely related to metabolic disorders of lipids and their derivatives. Lipids and their mediators play both a pro-inflammatory and anti-inflammatory role in chronic inflammatory bronchopulmonary pathology. In particular, free fatty acids (FFAs) perform important signaling and regu latory functions in the body, coordinating metabolic and immune relationships. The mechanism that potentially binds FFAs and inflammatory reactions involves the activation of their receptors (FFAR – free fatty acid receptor), which are expressed on the cells of the respiratory tract, as well as on nerve and immune cells. Currently, FFARs are considered attractive targets in the treatment of chronic bronchopulmonary pathology, since modulation of their activity through the use of alimentary polyunsaturated fatty acids (PUFA) can affect the activity and resolution of neuroimmune inflammation in the bronchopulmonary system. However, controversial issues regarding their effectiveness and dose standardization of PUFA continue to limit their widespread use. This review summarizes the literature data on the role of medium- and longchain FFAs in the body’s immunoregulation in normal conditions and in chronic bronchopulmonary pathology. Data on medium and long chain FFA receptors – FFAR1 and FFAR4, FFAR-mediated signaling pathways in the regulation of metabolism and immune responses are systematized. The perspective and complex issues of the use of fatty acids in the treatment of chronic bronchopulmonary pathology are discussed.
... Endocannabinoids are bioactive lipids that activate Gprotein-coupled receptors to modulate multiple processes in living organisms, including inflammation. Endocannabinoids include anandamide, palmitoylethanolamide, and OEA 14,15 . OEA, a derivative of the metabolism of oleic acid, is synthesized mainly in small intestine cells, liver and adipose tissues, and neurons. ...
Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils.
... N erve growth factor (NGF), the prototype of neurotrophins' family, plays pleiotropic effects in differentiation, growth and maintenance of neurons during development and adulthood [1] . Since the first observation of NGF activity on mast cells, a sequela of works corroborated to define NGF as a crucial player in the neuro-endocrineimmune system interactions [2][3] . Several studies focused on the developing of neuroprotective and immunomodulatory strategies for the cure of neurodegenerative and chronic immune related disorders [4] . ...
Aim:
To develop an experimental model of endogenous nerve growth factor (NGF) deprivation by retrobulbar administration of purified neutralizing anti-NGF antibodies in young Sprague-Dawley rats and provide further information on NGF expression in the retina and cornea.
Methods:
Sixty old pathogen-free Sprague Dawley rats (p14, post-natal days) were treated with repeated retrobulbar injections of neutralizing anti-NGF (2 µL, 100 µg/mL, every 3d). After 2wk (p28), retinal and corneal tissues were investigated for morphological, biochemical, and molecular expression of trkANGFR by using Western blotting or immunofluorescence. Rhodopsin as well as protein profile expression were also investigated.
Results:
Chronic retrobulbar neutralizing anti-NGF antibodies changed the distribution of trkANGFR immunoreactivity at retinal level, while no changes were detected for global trkANGFR protein expression. By contrary, the treatment resulted in the increase of corneal trkANGFR expression. Retinal tissues showed a decreased rhodopsin expression as well as reduced number of both rhodopsin expressing and total retinal cells, as observed after single cell extraction. A decreased expression of ICAM-1, IL-17 and IL-13 as well as an increased expression of IL-21 typified retinal extracts. No significant changes were observed for corneal tissues.
Conclusion:
The reduced availability of endogenous NGF, as produced by chronic retrobulbar anti-NGF administration, produce a quick response from retinal tissues, with respect to corneal ones, suggesting the presence of early compensatory mechanisms to protect retinal networking.
... Рекрутирование TLRs в липидные рафты и их димеризация частично связаны с НАДФН-оксидазозависимой генерацией активных форм кислорода и образовани- ем активных форм азота [24]. Развитие оксидативного стресса сопровождается образованием окисленных форм фосфолипидов, которые являются маркерами различных хронических заболеваний и патологических состояний [60,61]. Накопление в интиме артерий липопротеинов низкой плотности сопровождается образованием Ox-PLs, способствующих развитию метаболических нарушений [60]. ...
... Развитие оксидативного стресса сопровождается образованием окисленных форм фосфолипидов, которые являются маркерами различных хронических заболеваний и патологических состояний [60,61]. Накопление в интиме артерий липопротеинов низкой плотности сопровождается образованием Ox-PLs, способствующих развитию метаболических нарушений [60]. Метаболическая эндотоксемия как результат диеты с высоким содержанием жиров приводит к развитию оксидативного стресса и образованию Ox-PLs, которые посредством воспалительных путей CD36-TLR4-TLR6 или CD14-TLR4-MD2 индуцируют развитие хронического воспаления [56]. ...
Toll-like receptors (TLRs) are important players in innate and adaptive immune responses involved in the initiation of the inflammatory process in response to the stimulating influence of endogenous (аllarmine) and exogenous ligands (pathogens viruses, bacteria, fungi). It has now become apparent that not only viral and bacterial infections but non-infectious inflammatory diseases are accompanied by the activation of inflammatory response systems and the development of chronic inflammation associated with disorders in the regulation of the TLRs system. In this regard, the ligand-independent activation of TLRs, which occurs with the participation of lipids, is actively studied. Their signalling functions of TLRs implemented in unique microdomains does membrane lipid rafts that coordinate many cellular processes. The ability to activate TLRs has been found for saturated fatty acids (SFAs), both exogenous and endogenous. On the other hand, TLRs can be inhibited by omega-3 polyunsaturated fatty acids (PUFAs), which can block the inflammatory process. The activation of TLRs triggers a signal cascade that induces the production of reactive oxygen and nitrogen species. The development of oxidative stress is accompanied by the formation of oxidized forms of phospholipids (Ox-PLs), which also induce the development of chronic inflammation. At the same time, Ox-PLs is characterized not only by pro-inflammatory but also anti-inflammatory activity, which necessitates in-depth studies of their role in the implementation of these processes. This review article discusses the mechanisms by which SFAs, PUFAs, and Ox-PLs modulate TLRs activation in lipid rafts. Research into the details of these mechanisms will contribute to the development of a strategy to reduce the risk of chronic diseases caused by inflammatory reactions mediated by TLRs.
... While the total consumption of marine and plant n-3 Journal of Obesity polyunsaturated fatty acids in contemporary society is significantly reduced [7,76]. Another reason for PUFAs reduction is deterioration in the plasmalogen synthesis [77]. Plasmalogens are a subclass of phospholipids characterized by having a vinyl ether bond linking the fatty aldehyde to the glycerol molecule in the 1position and a fatty acyl bond in the 2-position. ...
... Secondary deficiency of plasmalogens triggered by their synthesis reduction or their degradation growth is associated with metabolic and inflammatory disorders such as cardiac diseases and diabetes mellitus [77]. e specificity of choline plasmalogens as a sensitive biomarker of an atherogenic state was confirmed. ...
... Plasmalogen oxidation products are not capable of further initiation of lipid peroxidation processes. Another important function of plasmalogens is their participation in cell metabolism and transmembrane transport of FAs. e presence of PUFAs in the side chains of plasmalogens preconfigures their significant depositing function [77]. Cholesterol esterification depends on the level of plasmalogens. ...
Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.
... Fatty acid ethanolamides (FAEs) are lipid mediators that exist ubiquitously in animal tissues. Anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA) are the three primary FAEs that play key roles in the regulation of various physiological and pathological processes [1]. AEA and another endogenous lipid 2-arachidonoyl-sn-glycerol (2-AG) are the main members of endocannabinoids, which perform important roles in the treatment of obesity and metabolic disorders through cannabinoid receptors (CBRs) [2]. ...
Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA–PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.
... TRP channels expressed in the airways may be activated by both exogenous and endogenous factors. A number of these triggers play an important role in the development and progression of asthma [34,35]. ...
Asthma is a chronic heterogeneous disease characterized by chronic inflammation and bronchial hyperreactivity. Neurogenic inflammation is one of the important causes of hyperreactivity. Dysfunction of transient receptor potential (TRP) ion channels underlies the development of neurogenic inflammation, bronchial hyperreactivity and respiratory symptoms of asthma such as bronchospasm and cough. TRP channels are expressed in the respiratory tract. Their activation is mediated by endogenous and exogenous factors involved in the pathogenesis of asthma. The study of functioning and regulation of TRP channels is relevant, as they could be important therapeutic targets for asthma. The aim of the review is to summarize modern ideas about the mechanisms of functioning and regulation of members of the TRP channel superfamily, the role of which in lung pathology and physiology are the best studied.
