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

International Journal of Molecular Sciences

Abraham Weizman¹  Maya Azrad²  Leo Veenman²  Moshe Gavish²  Nidal Zeineh² 

[1] Research Unit at Geha Mental Health Center and the Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva 4910002, Israel;The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa 31096, Israel;

关键词: TSPO ligands;    neuroinflammation;    microglial activation;    lipopolysaccharide (LPS);    cyclooxygenase-2 (COX-2);    inducible nitric oxide synthase (iNOS);    nitric oxide (NO);   

DOI  :  10.3390/ijms20030594

来源: DOAJ

【 摘 要 】

The 18 kDa Translocator Protein (TSPO) is a marker for microglial activation as its expression is enhanced in activated microglia during neuroinflammation. TSPO ligands can attenuate neuroinflammation and neurotoxicity. In the present study, we examined the efficacy of new TSPO ligands designed by our laboratory, MGV-1 and 2-Cl-MGV-1, in mitigating an in vitro neuroinflammatory process compared to the classic TSPO ligand, PK 11195. We exposed BV-2 microglial cells to lipopolysaccharide (LPS) for 24 h to induce inflammatory response and added the three TSPO ligands: (1) one hour before LPS treatment (pretreatment), (2) simultaneously with LPS (cotreatment), and (3) one hour after LPS exposure (post-treatment). We evaluated the capability of TSPO ligands to reduce the levels of three glial inflammatory markers: cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO). We compared the effects of the two novel ligands to PK 11195. Both 2-Cl-MGV-1 and MGV-1 reduced the levels of glial COX-2, iNOS, and NO in LPS-treated BV-2 cells more efficiently than PK 11195. Notably, even when added after exposure to LPS, all ligands were able to suppress the inflammatory response. Due to their pronounced anti-inflammatory activity, 2-Cl-MGV-1 and MGV-1 may serve as potential therapeutics in neuroinflammatory and neurodegenerative diseases.

【 授权许可】

Unknown