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Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

1
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia
2
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia
3
SREC PFUR Peoples’ Friendship University of Russia (RUDN University), Moscow 117198, Russia
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1553; https://doi.org/10.3390/cells8121553
Received: 2 November 2019 / Revised: 22 November 2019 / Accepted: 29 November 2019 / Published: 1 December 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
A phenomenon of endotoxin tolerance where prior exposure of cells to minute amounts of lipopolysaccharide (LPS) causes them to become refractory to a subsequent high-amount endotoxin challenge is well described for innate immune cells such as monocytes/macrophages, but it is still obscure for brain cells. We exposed primary rat cortical astrocytes to a long-term low-grade concentration of LPS, followed by stimulation with a middle-grade concentration of LPS. Inflammatory markers, i.e., pro-inflammatory cytokine TNFα, inducible enzymes COX-2 and iNOS, anti-inflammatory cytokine interleukin 10 (IL-10) detected at the mRNA and protein levels reveal similarities between astrocytes and macrophages in the model, i.e., tolerance in pro-inflammatory markers and priming in IL-10. Long-term or short-term treatment with IL-10 does not change cell sensitivity for LPS, which makes doubtful its involvement in the mechanisms of cell tolerance development. Significant changes occur in the oxylipin profiles measured by UPLC-MS/MS analysis. The priming occurs in the following compounds: 11-HETE, PGD2, PGE2, cyclopentenone prostaglandins, and TXB2. Tolerance is observed for 12-HHT, PGF, and 6-keto-PGF. As far as we know, this is the first report on changes in oxylipin profiles in the endotoxin tolerance model. The data can greatly improve the understanding of oxylipins’ role in inflammatory and resolution processes in the brain and mechanisms of astrocyte involvement in neuroinflammation. View Full-Text
Keywords: astrocytes; inflammation; endotoxin tolerance; eicosanoids; oxylipins; interleukin-10 astrocytes; inflammation; endotoxin tolerance; eicosanoids; oxylipins; interleukin-10
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Chistyakov, D.V.; Astakhova, A.A.; Azbukina, N.V.; Goriainov, S.V.; Chistyakov, V.V.; Sergeeva, M.G. Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins. Cells 2019, 8, 1553.

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