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The protective effect of the TSPO ligands 2,4-Di-Cl-MGV-1, CB86, and CB204 against LPS-induced M1 pro-inflammatory activation of microglia

Authors :
Rafi Nagler
Moshe Gavish
Abraham Weizman
Nunzio Denora
Massimo Franco
Sheelu Monga
Valentino Laquintana
Ilan Marek
Sukhdev Singh
Source :
Brain, Behavior, & Immunity-Health, Vol 5, Iss, Pp 100083-(2020), Brain, Behavior, & Immunity-Health
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

We have shown previously, that the 18 ​kDa translocator protein (TSPO) synthetic ligands quinazoline derivatives (2-Cl-MGV-1 and MGV-1) can inhibit activation of in BV-2 microglial cells. In the present study we assessed the impact of novel TSPO ligands on lipopolysaccharide (LPS)-induced microglial activation as expressed by release of pro-inflammatory molecules, including cytokines [interleukin-6 (IL-6), IL-1β, interferon- γ (IFN-γ)] nitric oxide (NO), CD8, and cyclo-oxygenase-2 (COX-2). The TSPO ligands 2,4-Di-Cl-MGV-1, CB86, and CB204 counteracted with the LPS-induced microglial activation. Exposure to LPS along with the TSPO ligand 2,4-Di-Cl-MGV-1 (25 ​μM) reduced significantly the release of NO by 24-, IL-6 by 14-, IL-β by 14-, IFN- γ by 6-, and TNF-α by 29-folds, respectively. In contrast to the anti-neuroinflammatory effect of the TSPO ligands, the effect of diclofenac sodium (DS; 25 ​μM) did not reach statistical significance. No alterations in IL-10 and IL-13 were detected (M2 anti-inflammatory pathway) during the inhibition of M1 pro-inflammatory pathway.

Details

ISSN :
26663546
Volume :
5
Database :
OpenAIRE
Journal :
Brain, Behavior, & Immunity - Health
Accession number :
edsair.doi.dedup.....36707c92867775956d571551ac6c2b69
Full Text :
https://doi.org/10.1016/j.bbih.2020.100083