Cargando…

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

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, a...

Descripción completa

Detalles Bibliográficos
Autores principales: Shimoyama, Shuji, Furukawa, Tomonori, Ogata, Yoshiki, Nikaido, Yoshikazu, Koga, Kohei, Sakamoto, Yui, Ueno, Shinya, Nakamura, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752844/
https://www.ncbi.nlm.nih.gov/pubmed/31536603
http://dx.doi.org/10.1371/journal.pone.0222861
_version_ 1783452797830692864
author Shimoyama, Shuji
Furukawa, Tomonori
Ogata, Yoshiki
Nikaido, Yoshikazu
Koga, Kohei
Sakamoto, Yui
Ueno, Shinya
Nakamura, Kazuhiko
author_facet Shimoyama, Shuji
Furukawa, Tomonori
Ogata, Yoshiki
Nikaido, Yoshikazu
Koga, Kohei
Sakamoto, Yui
Ueno, Shinya
Nakamura, Kazuhiko
author_sort Shimoyama, Shuji
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6752844
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-67528442019-09-27 Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2 Shimoyama, Shuji Furukawa, Tomonori Ogata, Yoshiki Nikaido, Yoshikazu Koga, Kohei Sakamoto, Yui Ueno, Shinya Nakamura, Kazuhiko PLoS One Research Article 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. Public Library of Science 2019-09-19 /pmc/articles/PMC6752844/ /pubmed/31536603 http://dx.doi.org/10.1371/journal.pone.0222861 Text en © 2019 Shimoyama et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shimoyama, Shuji
Furukawa, Tomonori
Ogata, Yoshiki
Nikaido, Yoshikazu
Koga, Kohei
Sakamoto, Yui
Ueno, Shinya
Nakamura, Kazuhiko
Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title_full Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title_fullStr Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title_full_unstemmed Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title_short Lipopolysaccharide induces mouse translocator protein (18 kDa) expression via the AP-1 complex in the microglial cell line, BV-2
title_sort lipopolysaccharide induces mouse translocator protein (18 kda) expression via the ap-1 complex in the microglial cell line, bv-2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752844/
https://www.ncbi.nlm.nih.gov/pubmed/31536603
http://dx.doi.org/10.1371/journal.pone.0222861
work_keys_str_mv AT shimoyamashuji lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT furukawatomonori lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT ogatayoshiki lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT nikaidoyoshikazu lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT kogakohei lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT sakamotoyui lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT uenoshinya lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2
AT nakamurakazuhiko lipopolysaccharideinducesmousetranslocatorprotein18kdaexpressionviatheap1complexinthemicroglialcelllinebv2