Comparison of TLR3- and TLR4-mediated signaling cascades in glial cellsстатьяТезисы
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 16 января 2019 г.
Аннотация:Toll-like receptor (TLR) mediated signaling cascades play crucial role in neuroinflammation and therefore may be targets for manipulation with therapy purposes. Although many efforts have made, molecular mechanisms of TLR-mediated signaling in astrocytes is largely unknown, especially relative to regulation of signaling lipids release. Many of signaling lipids belong to a family of resolution of inflammation processes factors, and low molecular weight substances can regulate their synthesis, therefore the aim of our study was comparison of signaling lipids synthesis in course of stimulation by lipopolysaccharide (LPS, a TLR4 agonist) and poly I:C (PIC, a TLR3 agonist). Primary astrocytes from newborn rats were cultured 12 days before experiments; Western blot was used for detection of TLR signaling pathway proteins and enzymes of lipid synthesis. Cell-free culture media were taken for solid-phase lipid extraction; lipid mediators (25 lipids) were analyzed by 8040 series UPLC-MS/MS (Shimadzu) with 4 MS standards. Time-course cellular responses (1,2, 4, 6, 8, 12, 24 h) for stimulation with LPS and PIC were compared. We obtained that three pathways of polyunsaturated acids (PUFAs) transformation (COXs, 12/15 LOX, cytP450) are involved in astrocytes responses. 13 substances are released in significant amounts. Releases of PUFAs or their non-enzymatic derivatives are similar for both tested agonists. TLR3 activation significantly induces enzyme-mediated metabolism in comparison with TLR4 activation. Both agonists induce shift of PUFAs metabolism from proinflammatory to resolution substances. Supported by RSF (№ 16-15-10298).