The TSPO Ligands 2-Cl-MGV-1, MGV-1, and PK11195 Differentially Suppress the Inflammatory Response of BV-2 Microglial Cell to LPS

Azrad, Maya; Zeineh, Nidal; Weizman, Abraham; Veenman, Leo; Gavish, Moshe

doi:10.3390/ijms20030594

Cited by 31 publications

(41 citation statements)

References 61 publications

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“…Additionally, the authors concluded that the neuroprotective effect of Emapunil might be associated with the partial alteration of neurosteroid levels, which can counteract neuroinflammatory responses [65]. Together with other studies applying TSPO ligands for the treatment of brain damage, this investigation showed promising results about exploiting TSPO as a possible therapeutic target for α-synucleinopathies [28,66]. However, greater efforts must be made to fully disclose the influence of TSPO ligands on dopaminergic degeneration.…”

Section: Tspo and Parkinson Disease (Pd)mentioning

confidence: 79%

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

Dimitrova-Shumkovska

Krstanoski

Veenman

2020

Cells

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Neuroinflammation and cell death are among the common symptoms of many central nervous system diseases and injuries. Neuroinflammation and programmed cell death of the various cell types in the brain appear to be part of these disorders, and characteristic for each cell type, including neurons and glia cells. Concerning the effects of 18-kDa translocator protein (TSPO) on glial activation, as well as being associated with neuronal cell death, as a response mechanism to oxidative stress, the changes of its expression assayed with the aid of TSPO-specific positron emission tomography (PET) tracers’ uptake could also offer evidence for following the pathogenesis of these disorders. This could potentially increase the number of diagnostic tests to accurately establish the stadium and development of the disease in question. Nonetheless, the differences in results regarding TSPO PET signals of first and second generations of tracers measured in patients with neurological disorders versus healthy controls indicate that we still have to understand more regarding TSPO characteristics. Expanding on investigations regarding the neuroprotective and healing effects of TSPO ligands could also contribute to a better understanding of the therapeutic potential of TSPO activity for brain damage due to brain injury and disease. Studies so far have directed attention to the effects on neurons and glia, and processes, such as death, inflammation, and regeneration. It is definitely worthwhile to drive such studies forward. From recent research it also appears that TSPO ligands, such as PK11195, Etifoxine, Emapunil, and 2-Cl-MGV-1, demonstrate the potential of targeting TSPO for treatments of brain diseases and disorders.

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Section: Tspo and Parkinson Disease (Pd)mentioning

confidence: 79%

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

Dimitrova-Shumkovska

Krstanoski

Veenman

2020

Cells

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“…TSPO has low affinity for these ligands (both approximately 825 nM) due to the elongation of the alkyl side chains, which reduces their lethal effects as compared to the classical TSPO ligands as described previously (21,22). The anti-inflammatory effects of MGV-1 and 2-Cl-MGV-1 were described previously (23).…”

Section: Methodsmentioning

confidence: 89%

“…Initially, two concentrations of the ligands were used based on preliminary studies, 1 and 25 μM final concentrations. Eventually, the chosen final concentration of the ligands in the current study was 25 μM, as used previously (22,23). Following incubation, the cells were exposed to CS for 30 and 60 min in order to optimize the cell death assays.…”

Section: Methodsmentioning

confidence: 99%

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18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study

Nagler

Zeineh

Azrad

et al. 2020

In Vivo

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Background: Cigarette smoke (CS) can induce cellular damage via alterations in 18 kDa translocator protein (TSPO)-related functions, leading to cardiovascular diseases. The current study focused on the possible protective effect of TSPO ligands against CS-induced damage to cardiac cells. Materials and Methods: H9C2 Cardiomyocyte cell line of rat origin was pre-treated with TSPO ligands. Cell death, TSPO binding, and TSPO protein expression levels were assessed following 30-min CS exposure with/without TSPO ligands. Results: CS exposure of H9C2 cells significantly incensed cell death (by 26%, p<0.001). Pre-treatment with TSPO ligands at two concentrations prevented cell death. Neither CS nor ligands affected TSPO protein expression in H9C2 cells. CS led to increased cell death and reduced TSPO binding. Conclusion: Reduced TSPO binding may have a role in CS-induced cell death, and TSPO ligand MGV-1 can prevent suppression of TSPO binding and corresponding cell death. These results may be relevant to treatment of cardiovascular diseases associated with CS. 549

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“…The present study was performed to reveal to what extent glycine affected the viability, activation state and secretory activity of microglial cells during inflammation. BV-2 cells were stressed with a combination of LPS and IFN-γ over 24 h. LPS is the most common pro-inflammatory stimulus and causes inflammatory reactions in primary microglia and BV-2 cells [17,18], and IFN-γ is released during CNS injury [18][19][20]. Approximately 90% of the genes induced in BV-2 cells after LPS exposure were also found in primary microglia and showed similar reaction patterns [21], which warrants this cell line as a suitable experimental model.…”

Section: Discussionmentioning

confidence: 99%

Effect of Glycine on BV-2 Microglial Cells Treated with Interferon-γ and Lipopolysaccharide

Egger

Jakab

Fuchs

et al. 2020

IJMS

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Microglia are first-line defense antigen-presenting phagocytes in the central nervous system. Activated microglial cells release pro-inflammatory cytokines and can trigger an oxidative burst. The amino acid glycine exerts anti-inflammatory, immunomodulatory and cytoprotective effects and influences cell volume regulation. This study aimed to investigate the role of glycine in the modulation of inflammatory processes in mouse BV-2 microglial cells. Inflammatory stress was induced by lipopolysaccharide/interferon-γ (LPS/IFN-γ) treatment for 24 h in the absence or presence of 1 or 5 mM glycine. Cells were analyzed by flow cytometry for cell volume, side scatter, apoptosis/necrosis and expression of activation-specific surface markers. Apoptosis progression was monitored by life cell imaging. Reduced glutathione/oxidized glutathione (GSH/GSSG) ratios and release of the pro-inflammatory cytokines IL-6 and TNF-α were measured using luminescence-based assays and ELISA, respectively. We found that LPS/IFN-γ-induced apoptosis was decreased and the fraction of living cells was increased by glycine. Expression of the surface markers CD11b, CD54 and CD80 was dose-dependently increased, while IL-6 and TNF-α release was not altered compared to LPS/IFN-γ-treated cells. We showed that in BV-2 microglial cells glycine improves viability and counteracts deleterious responses to LPS/IFN-γ, which might be relevant in neurodegenerative processes associated with inflammation, like Alzheimer’s or Parkinson’s disease.

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The TSPO Ligands 2-Cl-MGV-1, MGV-1, and PK11195 Differentially Suppress the Inflammatory Response of BV-2 Microglial Cell to LPS

Cited by 31 publications

References 61 publications

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update

18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study

Effect of Glycine on BV-2 Microglial Cells Treated with Interferon-γ and Lipopolysaccharide

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