Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC117910.15690/vramn1179IMMUNOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ИММУНОЛОГИИResearch ArticleThe role of lipids in the signaling mechanisms of toll-like receptorsРоль липидов в механизмах сигнализации толл-подобных рецепторовhttps://orcid.org/0000-0001-5018-02713006-5614KytikovаO. Yu.КытиковаО. Ю.
Russian Federation

MD, PhD

д.м.н.

kytikova@yandex.ruhttps://orcid.org/0000-0002-6058-201X5888-6099NovgorodtsevaT. P.НовгородцеваТ. П.
Russian Federation

PhD in Biology, Professor

д.б.н., профессор

nauka@niivl.ruhttps://orcid.org/0000-0003-4130-88994997-3432DenisenkoYu. K.ДенисенкоЮ. К.
Russian Federation

MD in Biology

д.б.н.

karaman@inbox.ruhttps://orcid.org/0000-0002-2492-31983446-4852AntonyukM. V.АнтонюкМ. В.
Russian Federation

MD, PhD, Professor

д.м.н., профессор

antonyukm@mail.ruhttps://orcid.org/0000-0002-6413-98407869-1692GvozdenkoT. A.ГвозденкоТ. А.
Russian Federation

MD, PhD, Professor

д.м.н., профессор

vfdnz@mail.ruFar Eastern Scientific Center of Physiology and Pathology of RespirationДальневосточный научный центр физиологии и патологии дыхания151220207565855931101202008122020Copyright ©; 2020, "Paediatrician" Publishers LLCCopyright ©; 2020, Издательство "Педиатръ"2020"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1179

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.

Толл-подобные рецепторы (TLRs) являются важными участниками врожденных и адаптивных иммунных реакций, вовлеченных в инициацию воспалительного процесса в ответ на стимулирующее влияние эндогенных (аллармины) и экзогенных (патогены вирусов, бактерий, грибов) лигандов. В настоящее время стало очевидным, что не только вирусные и бактериальные инфекции, но и неинфекционные воспалительные заболевания сопровождаются активацией систем воспалительного ответа и развитием хронического воспаления, связанного с нарушениями в регуляции системы TLRs. В связи с этим активно изучается лиганд-независимая активация TLRs, которая происходит с участием липидов. Свои сигнальные функции TLRs реализуют в уникальных микродоменах цитоплазматической мембраны — липидных рафтах, координирующих множество клеточных процессов. Способность к активации TLRs обнаружена для насыщенных жирных кислот (SFAs), как экзогенных, так и эндогенных. С другой стороны, TLRs могут быть ингибированы омега-3-полиненасыщенными жирными кислотами (PUFAs), что способствует блокированию воспалительного процесса. В результате активации TLRs запускается сигнальный каскад, который индуцирует производство активных форм кислорода и азота. Развитие оксидативного стресса сопровождается образованием окисленных форм фосфолипидов (Ox-PLs), которые также индуцируют развитие хронического воспаления. В то же время для Ox-PLs характерна не только провоспалительная, но и противовоспалительная активность, что обусловливает необходимость проведения глубоких исследований их роли в реализации данных процессов. В представленной обзорной статье рассматриваются и обсуждаются механизмы, с помощью которых SFAs, PUFAs и Ox-PLs модулируют активацию TLRs в липидных рафтах. Проведение научных исследований по детализации этих механизмов будет способствовать разработке стратегии снижения риска хронических заболеваний, которые вызваны воспалительными реакциями, опосредованными TLRs.

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