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Translocator Protein 18 kDa Negatively Regulates Inflammation in Microglia

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Abstract

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein. Although TSPO expression is up-regulated during neuroinflammation, the role of TSPO and its signaling mechanisms in regulation of neuroinflammation remains to be elucidated at the molecular level. Here we demonstrate that TSPO is a negative regulator of neuroinflammation in microglia. Over-expression of TSPO decreased production of pro-inflammatory cytokines upon lipopolysaccharide treatment while TSPO knock-down had the opposite effect. Anti-inflammatory activity of TSPO is also supported by increased expression of alternatively activated M2 stage-related genes. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism. We also provide the evidence that the repressive activity of TSPO is at least partially mediated by the attenuation of NF-κB activation. Neurodegenerative diseases are characterized by loss of specific subsets of neurons at the particular anatomical regions of the central nervous system. Cause of neuronal death is still largely unknown, but it is becoming clear that neuroinflammation plays a significant role in the pathophysiology of neurodegenerative diseases. Understanding the mechanisms underlying the inhibitory effects of TSPO on neuroinflammation can contribute to the therapeutic design for neurodegenerative diseases.

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Acknowledgments

We are grateful to Dr. Michael J. Zigmond (University of Pittsburgh) for providing MN9D cells. This work was supported by the DGIST Convergence Science Center Program (14-BD-04) of the Ministry of Science, ICT and Future Planning of Korea.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Deebika Balu

    Present address: Department of Biological Sciences, University of Illinois, Chicago, IL, USA

  2. Sang Ryong Kim

    Present address: School of Life Sciences & Biotechnology, Institute of Life Science and Biotechnology, Brain Science and Engineering Institute, Kyungpook National University, Daegu, Korea

Authors and Affiliations

  1. Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea

    Keun-Ryung Bae, Hyun-Jung Shim, Sang Ryong Kim & Seong-Woon Yu

  2. Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA

    Deebika Balu

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  1. Keun-Ryung Bae
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Correspondence to Seong-Woon Yu.

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Bae, KR., Shim, HJ., Balu, D. et al. Translocator Protein 18 kDa Negatively Regulates Inflammation in Microglia. J Neuroimmune Pharmacol 9, 424–437 (2014). https://doi.org/10.1007/s11481-014-9540-6

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