Da Pozzo, Eleonora and Tremolanti, Chiara and Costa, Barbara and Giacomelli, Chiara and Milenkovic, Vladimir M. and Bader, Stefanie and Wetzel, Christian H. and Rupprecht, Rainer and Taliani, Sabrina and Da Settimo, Federico and Martini, Claudia (2019) Microglial Pro-Inflammatory and Anti-Inflammatory Phenotypes Are Modulated by Translocator Protein Activation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20 (18): 4467. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
A key role of the mitochondrial Translocator Protein 18 KDa (TSPO) in neuroinflammation has been recently proposed. However, little is known about TSPO-activated pathways underlying the modulation of reactive microglia. In the present work, the TSPO activation was explored in an in vitro human primary microglia model (immortalized C20 cells) under inflammatory stimulus. Two different approaches were used with the aim to (i) pharmacologically amplify or (ii) silence, by the lentiviral short hairpin RNA, the TSPO physiological function. In the TSPO pharmacological stimulation model, the synthetic steroidogenic selective ligand XBD-173 attenuated the activation of microglia. Indeed, it reduces and increases the release of pro-inflammatory and anti-inflammatory cytokines, respectively. Such ligand-induced effects were abolished when C20 cells were treated with the steroidogenesis inhibitor aminoglutethimide. This suggests a role for neurosteroids in modulating the interleukin production. The highly steroidogenic ligand XBD-173 attenuated the neuroinflammatory response more effectively than the poorly steroidogenic ones, which suggests that the observed modulation on the cytokine release may be influenced by the levels of produced neurosteroids. In the TSPO silencing model, the reduction of TSPO caused a more inflamed phenotype with respect to scrambled cells. Similarly, during the inflammatory response, the TSPO silencing increased and reduced the release of pro-inflammatory and anti-inflammatory cytokines, respectively. In conclusion, the obtained results are in favor of a homeostatic role for TSPO in the context of dynamic balance between anti-inflammatory and pro-inflammatory mediators in the human microglia-mediated inflammatory response. Interestingly, our preliminary results propose that the TSPO expression could be stimulated by NF-kappa B during activation of the inflammatory response.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BENZODIAZEPINE-RECEPTOR-LIGAND; LONG RESIDENCE TIME; 18 KDA; ANXIOLYTIC ETIFOXINE; TSPO-LIGANDS; MITOCHONDRIAL; APOPTOSIS; CELLS; LIPOPOLYSACCHARIDE; REGENERATION; translocator protein 18 KDa; human microglial cells; neuroinflammation; interleukins; neurosteroids |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 09:50 |
| Last Modified: | 06 Apr 2020 09:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26280 |
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