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Int. J. Mol. Sci. 2018, 19(1), 113; doi:10.3390/ijms19010113

Rosiglitazone as a Modulator of TLR4 and TLR3 Signaling Pathways in Rat Primary Neurons and 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
Research Center of Neurology, Moscow 125367, Russia
*
Author to whom correspondence should be addressed.
Received: 22 November 2017 / Revised: 25 December 2017 / Accepted: 27 December 2017 / Published: 2 January 2018
(This article belongs to the Special Issue The Interleukins in Health and Disease)
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Abstract

An antidiabetic drug of the thiazolidinedione class, rosiglitazone (RG) demonstrates anti-inflammatory properties in various brain pathologies. The mechanism of RG action in brain cells is not fully known. To unravel mechanisms of RG modulation of toll-like receptor (TLR) signaling pathways, we compare primary rat neuron and astrocyte cultures stimulated with the TLR4 agonist lipopolysaccharide (LPS) and the TLR3 agonist poly I:C (PIC). Both TLR agonists induced tumor necrosis factor (TNFα) release in astrocytes, but not in neurons. Neurons and astrocytes released interleukin-10 (IL-10) and prostaglandin E2 (PGE2) in response to LPS and PIC. RG decreased TLR-stimulated TNFα release in astrocytes as well as potentiated IL-10 and PGE2 release in both astrocytes and neurons. RG induced phosphorylation of p38 and JNK MAPK (mitogen-activated protein kinase) in neurons. The results reveal new role of RG as a modulator of resolution of neuroinflammation. View Full-Text
Keywords: toll-like receptor (TLR); poly I:C (PIC); lipopolysaccharide (LPS); interleukin-10 (IL-10); tumor necrosis factor alpha (TNFα); mitogen-activated kinase (MAPK); rosiglitazone (RG); thiazolidinedione (TZD) toll-like receptor (TLR); poly I:C (PIC); lipopolysaccharide (LPS); interleukin-10 (IL-10); tumor necrosis factor alpha (TNFα); mitogen-activated kinase (MAPK); rosiglitazone (RG); thiazolidinedione (TZD)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chistyakov, D.V.; Azbukina, N.V.; Lopachev, A.V.; Kulichenkova, K.N.; Astakhova, A.A.; Sergeeva, M.G. Rosiglitazone as a Modulator of TLR4 and TLR3 Signaling Pathways in Rat Primary Neurons and Astrocytes. Int. J. Mol. Sci. 2018, 19, 113.

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