Abstract
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.
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28 April 2020
The original version of this article unfortunately contained mistakes in the Author Group section. Authors Dandan Zhou and Lei Ji were assigned to incorrect institutions.
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Supplement Fig. 1
Western blotting showed the PPAR-γ expression in the group treated with PK11195, FGIN-1-27, or TSPO overexpression alone. (PNG 40 kb)
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Zhou, D., Ji, L. & Chen, Y. TSPO Modulates IL-4-Induced Microglia/Macrophage M2 Polarization via PPAR-γ Pathway. J Mol Neurosci 70, 542–549 (2020). https://doi.org/10.1007/s12031-019-01454-1
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DOI: https://doi.org/10.1007/s12031-019-01454-1