Examining the Anti-Inflammatory Characteristics of Translocator Protein Through IL-10 Modulation

Abstract

Several central nervous system related diseases involve various cellular inflammation related components. Among others these components include increases in complement activation and synthesis of inflammatory signaling mediators. Therefore, several strategies for creating therapeutic benefit in patients has centered on targeting these cellular inflammatory mechanisms. One of these strategies has been to target the translocator protein (TSPO), which is an 18kDa outer mitochondrial membrane bound protein used in mediating transport of cholesterol into the inner mitochondrial membrane (Karlsetter, 2014). Recent studies have shown that activation of TSPO can induce a cellular anti-inflammatory response. The immunomodulation of the anti-inflammatory process is generally controlled by cytokines such as interleukin-10. So far, several protein, small molecule and peptide agonists, which stimulate the production of IL-10, have been elucidated. Recently Karlsetter et al displayed a cellular model where the potent inflammatory effects of lipopolysaccharide (LPS) were reduced with an increasing concentration of TSPO. This data and other evidence hint at a mechanism where TSPO induces an anti-inflammatory response by upregulating IL-10. Therefore I propose that IL-10 mRNA and IL-10 protein levels are elevated within immune cells when TSPO levels have been overexpressed. To test this, TSPO was stimulated with Etifoxine, a known TSPO ligand, and evaluated for increases in IL-10 mRNA and protein. Gene expression and protein production data showed that no concentration or incubation of Etifoxine was able to upregulate IL-10 mRNA or protein. Furthermore, stable overexpression of TSPO in a macrophage cell line was unable to induce any increase in IL-10 message levels. These results suggest that TSPO does not modulate IL-10 and its inflammatory effects.