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Open AccessArticle

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

1
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia
2
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia
3
SREC PFUR Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1780; https://doi.org/10.3390/ijms21051780
Received: 30 January 2020 / Revised: 1 March 2020 / Accepted: 3 March 2020 / Published: 5 March 2020
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2020)
Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus. View Full-Text
Keywords: rat astrocytes; oxylipins; eicosanoids; polarization; interleukins IL-4; IL-10; endotoxin tolerance; inflammation; LPS rat astrocytes; oxylipins; eicosanoids; polarization; interleukins IL-4; IL-10; endotoxin tolerance; inflammation; LPS
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MDPI and ACS Style

Chistyakov, D.V.; Gavrish, G.E.; Goriainov, S.V.; Chistyakov, V.V.; Astakhova, A.A.; Azbukina, N.V.; Sergeeva, M.G. Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS. Int. J. Mol. Sci. 2020, 21, 1780. https://doi.org/10.3390/ijms21051780

AMA Style

Chistyakov DV, Gavrish GE, Goriainov SV, Chistyakov VV, Astakhova AA, Azbukina NV, Sergeeva MG. Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS. International Journal of Molecular Sciences. 2020; 21(5):1780. https://doi.org/10.3390/ijms21051780

Chicago/Turabian Style

Chistyakov, Dmitry V.; Gavrish, Gleb E.; Goriainov, Sergei V.; Chistyakov, Viktor V.; Astakhova, Alina A.; Azbukina, Nadezda V.; Sergeeva, Marina G. 2020. "Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS" Int. J. Mol. Sci. 21, no. 5: 1780. https://doi.org/10.3390/ijms21051780

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