Comparison of TLR-4 mediated synthesis of oxylipins by microglia and astrocytesстатьяТезисы
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Дата последнего поиска статьи во внешних источниках: 23 января 2020 г.
Аннотация:Oxylipins formed from polyunsaturated fatty acids (PUFAs) are active players of inflammatory processes with pro- or anti-inflammatory roles. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways from x-6 (arachidonic (AA)) and x-3 (docosahexaenoic (DHA), eicosapentaenoic (EPA)) acids and also from essential fatty acids. Microglia and astrocytes are responsible for neuroinflammatory responses, but differences of oxylipin synthesis were not studied. Our aim was a comparison of microglia and astrocytes oxylipins synthesis in course of LPS activation (a TLR4 agonist). Primary astrocytes from newborn rats were cultured 12 days before experiments; microglia was isolated by “shaking method” according to the standard protocol. Western blot was used for detection of signaling pathway proteins. Cell-free culture media were taken for solid-phase lipid extraction. Oxylipins and PUFAs were analyzed by 8040 series UPLC-MS/MS (Shimadzu) with 16 standards. Astrocytes and microglia responses at 4 h and 24 h stimulations with LPS were compared. Totally we detected 43 substances upon our treatments. We obtained that microglia release significant amounts of EPA, DHA and AA in unstimulated cells that decreased under TLR stimulation and significant increase of appropriate acid derivatives via cyclooxygenase, lipoxygenase, or cytochrome P450 pathways. Astrocytes showed a weaker ability to release acids without stimulation, but activation of TLR signaling pathways resulted in release of oxylipins formed mainly via cyclooxygenase and cytochrome P450 pathways. Although most substances are common for microglia and astrocytes, such oxylipins as 9-HODE, 13-HDoHE, 16-HDoHE, PGA2, PGJ2 are formed principally by activated astrocytes. Data show new opportunities for the participation of oxylipins synthesis form microglia and astrocytes in regulation of TLR-mediated responses. Supported by RFBI 18-34-20100. *The authors marked with an asterisk equally contributed to the work.