TSPO Modulates IL-4-Induced Microglia/Macrophage M2 Polarization via PPAR-γ Pathway

• Published in: Journal of molecular neuroscience Vol. 70; no. 4; pp. 542 - 549
• Main Authors: Zhou, Dandan, Ji, Lei, Chen, Youguo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2020; Springer Nature B.V
• Subjects: Activation; Animals; Arginase - genetics; Arginase - metabolism; beta-N-Acetylhexosaminidases - genetics; beta-N-Acetylhexosaminidases - metabolism; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Cell Biology; Cell Differentiation; Cell Hypoxia; Cells, Cultured; Central nervous system; Cytoplasm; Damage; Degeneration; Enzyme-linked immunosorbent assay; Hypoxia; Indoleacetic Acids - pharmacology; Inflammation; Insulin-like growth factor I; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Interleukin 4; Interleukin-4 - metabolism; Ischemia; Isoquinolines - pharmacology; Lectins - genetics; Lectins - metabolism; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Markers; Mice; Mice, Inbred BALB C; Microglia; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Nerve growth factor; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; Neurochemistry; Neurodegeneration; Neurology; Neurosciences; Pathogenesis; Peroxisome proliferator-activated receptors; Polarization; PPAR gamma - metabolism; Proteins; Proteomics; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, GABA - genetics; Receptors, GABA - metabolism; Trophic factors; TSPO; Neonatal hypoxia-ischemia; M2; Microglia polarization; PPAR-γ
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-019-01454-1

Microglia activation has been reported to be associated with pathogenesis of neuroinflammation, central nervous system damage, and degeneration diseases. With various damage-associated molecules released, M1 polarization of microglia emerges early after injury and followed by M2 polarization. In this study, we demonstrate using a primary microglia polarization model that, during the M2 polarization of microglia, the protein expression of translocator protein (TSPO) was decreased and peroxisome proliferator–activated receptor (PPAR-γ) activation was observed. In addition, we found TSPO antagonist PK11195 treatment enhanced PPAR-γ expression in M2-polarized microglia, while TSPO agonist FGIN-1-27 and TSPO overexpression in microglia significantly suppressed PPAR-γ expression in both the cytoplasm and nucleus. Then, real-time quantitative PCR was used to detect the expression of M2 polarization markers in microglia after TSPO ligand treatment, the data showed that PK11195 promoted the expression of CD206, Arg-1, YM-1, and FIZZ-1 induced by interleukin-4 (IL-4), and FGIN-1-27 and TSPO overexpression inhibited the expression of these molecules. Furthermore, the release of BDNF, CNTF-1, IGF-1, and NGF-1 from microglia was determined by enzyme-linked immunosorbent assay; these trophic factors showed similar trends with expression of M2 polarization markers. Levels of BDNF, CNTF-1, IGF-1, and NGF-1 were obviously upregulated by PK11195 and downregulated by FGIN-1-27 and TSPO overexpression. We propose that IL-4 in the hypoxic ischemia brain site induces the M2 polarization of microglia, and TSPO inhibits the M2 polarization and trophic factor release through PPAR-γ pathway.