The role of lipids in the signaling mechanisms of toll-like receptors


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Abstract

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.

About the authors

O. Yu. Kytikovа

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Author for correspondence.
Email: kytikova@yandex.ru
ORCID iD: 0000-0001-5018-0271
SPIN-code: 3006-5614

MD, PhD

Russian Federation, Vladivostok

T. P. Novgorodtseva

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: nauka@niivl.ru
ORCID iD: 0000-0002-6058-201X
SPIN-code: 5888-6099

PhD in Biology, Professor

Russian Federation, Vladivostok

Yu. K. Denisenko

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: karaman@inbox.ru
ORCID iD: 0000-0003-4130-8899
SPIN-code: 4997-3432

MD in Biology

Russian Federation, Vladivostok

M. V. Antonyuk

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: antonyukm@mail.ru
ORCID iD: 0000-0002-2492-3198
SPIN-code: 3446-4852

MD, PhD, Professor

Russian Federation, Vladivostok

T. A. Gvozdenko

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: vfdnz@mail.ru
ORCID iD: 0000-0002-6413-9840
SPIN-code: 7869-1692

MD, PhD, Professor

Russian Federation, Vladivostok

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