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Article

Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes

1
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia
2
Laboratory of electrophysiology, Pirogov Russian National Research Medical University, Moscow 117997, Russia
3
Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Moscow 119234, Russia
4
SREC PFUR, Peoples’ Friendship University of Russia (RUDN University), Moscow 117198, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(9), 2793; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092793
Received: 27 August 2018 / Revised: 12 September 2018 / Accepted: 14 September 2018 / Published: 17 September 2018
Although many neurological and psychiatric disorders reveal clear sex-dependent variations, the molecular mechanism of this process is not clear enough. Astrocytes are involved in the response of neural tissue to injury and inflammation, produce steroid hormones, and sense steroid presence. To explore the hypothesis that astrocytes may participate in sex-mediated differences of inflammatory responses, we have examined whether male and female primary rat astrocytes show different responses to lipopolysaccharide (LPS) as a toll-like receptor 4 (TLR4) agonist. Levels of mRNA and proteins of tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and cyclooxygenase (COX)-2 were assessed using qPCR, immunoblotting, and ELISA. UPLC-MS/MS was used to detect prostaglandins (PGs). LPS stimulation resulted in different levels of cytokine production; more TNFα and less IL-10 were produced in female cells compared with male astrocytes. Although the levels of the COX-2 expression were not altered, LPS significantly induced the synthesis of PGs with notable sex-related differences. PGE2 and PGD2 were less and 6-keto-PGF was more upregulated in female astrocytes, and TXB2 had similar levels in cells obtained from males and females. Trilostane, an inhibitor of 3β-Hydroxysteroid dehydrogenase (3β-HSD), inhibited the LPS-induced TNFα production and the release of PGE2, PGD2, and 6-keto-PGF in female astrocytes. Thus, male and female astrocytes differentially respond to inflammatory challenges on the level of production of cytokines and steroid hormones. Sex-mediated differences in pro- and anti-inflammatory responses should be taken into consideration for the effective treatment of disorders with neuroinflammation. View Full-Text
Keywords: sex difference; neuroinflammation; COX-2; 3β-HSD; astrocytes; trilostane; LPS; TLR4; IL-10; TNFα sex difference; neuroinflammation; COX-2; 3β-HSD; astrocytes; trilostane; LPS; TLR4; IL-10; TNFα
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MDPI and ACS Style

Chistyakov, D.V.; Azbukina, N.V.; Astakhova, A.A.; Goriainov, S.V.; Chistyakov, V.V.; Sergeeva, M.G. Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes. Int. J. Mol. Sci. 2018, 19, 2793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092793

AMA Style

Chistyakov DV, Azbukina NV, Astakhova AA, Goriainov SV, Chistyakov VV, Sergeeva MG. Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes. International Journal of Molecular Sciences. 2018; 19(9):2793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092793

Chicago/Turabian Style

Chistyakov, Dmitry V., Nadezda V. Azbukina, Alina A. Astakhova, Sergei V. Goriainov, Viktor V. Chistyakov, and Marina G. Sergeeva. 2018. "Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes" International Journal of Molecular Sciences 19, no. 9: 2793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092793

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