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Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2


Autoři: Shuji Shimoyama aff001;  Tomonori Furukawa aff002;  Yoshiki Ogata aff002;  Yoshikazu Nikaido aff002;  Kohei Koga aff002;  Yui Sakamoto aff003;  Shinya Ueno aff001;  Kazuhiko Nakamura aff001
Působiště autorů: Research Center for Child Mental Development, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan aff001;  Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan aff002;  Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222861

Souhrn

It has been reported that neuroinflammation occurs in the central nervous system (CNS) in patients with neuropathic pain, Alzheimer’s disease and autism spectrum disorder. The 18-kDa translocator protein TSPO is used as an imaging target in positron emission tomography to detect neuroinflammation, and its expression is correlated with microglial activation. However, the mechanism underlying the transcriptional regulation of Tspo induced by inflammation is not clear. Here, we revealed that lipopolysaccharide (LPS) -induced Tspo expression was activated by the AP-1 complex in a mouse microglial cell line, BV-2. Knockdown of c-Fos and c-Jun, the components of AP-1, reduced LPS-induced Tspo expression. Furthermore, the enrichment of Sp1 in the proximal promoter region of Tspo was increased in the presence of LPS. In addition, the binding of histone deacetylase 1 (HDAC1) to the enhancer region, which contains the AP-1 site, was decreased by LPS treatment, but there were no significant differences in HDAC1 binding to the proximal promoter region with or without LPS. These results indicated that HDAC1 is involved not in the proximal promoter region but in the enhancer region. Our study revealed that inflammatory signals induce the recruitment of AP-1 to the enhancer region and Sp1 to the proximal promoter region of the Tspo gene and that Sp1 may regulate the basal expression of Tspo.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Glial cells – Microglial cells – Cellular structures and organelles – Biochemistry – Bioenergetics – Energy-producing organelles – Mitochondria – Nucleic acids – RNA – Non-coding RNA – Promoter regions – Proteins – DNA-binding proteins – Transcription factors – Regulatory proteins – Genetics – Gene expression – Gene regulation – Transcriptional control – Small interfering RNAs – DNA


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