Bidirectional modulation of TNF-alpha transcription via alpha- and beta-adrenoceptors in cultured astrocytes from rat spinal cord

Morimoto, Kohei; Kitano, Taisuke; Eguchi, Ryota; Otsuguro, Ken-ichi

Bidirectional modulation of TNF-alpha transcription via alpha- and beta-adrenoceptors in cultured astrocytes from rat spinal cord

Morimoto, Kohei; Kitano, Taisuke; Eguchi, Ryota et al.

Biochemical and biophysical research communications, 2020, 528(1), 78-84

Permalink : https://hdl.handle.net/2115/82212

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アクセス権	open access
URI	https://hdl.handle.net/2115/82212
タイトル	Bidirectional modulation of TNF-alpha transcription via alpha- and beta-adrenoceptors in cultured astrocytes from rat spinal cord
著者	Morimoto, Kohei ; Kitano, Taisuke ; Eguchi, Ryota ; Otsuguro, Ken-ichi
著者名 Morimoto, Kohei
著者名 Kitano, Taisuke
e-Rad_Researcher 10846067 著者名 Eguchi, Ryota
e-Rad_Researcher 40344494 著者名 Otsuguro, Ken-ichi
言語	英語
キーワード	Astrocyte
	Noradrenaline
	Adrenoceptors
	TNF-alpha
	Transcription factor
発行日	2020-07-12
出版者	Elsevier
収録物名	Biochemical and biophysical research communications
巻(号)	528(1)
ページ	78-84
抄録	Noradrenaline (NA) suppresses TNF-alpha production via beta-adrenoceptors (ARs) in brain astrocytes. However, the downstream pathways from beta-ARs, and the involvement of alpha-ARs, remains unknown. In this study, we investigated the AR-mediated regulation of TNF-alpha mRNA levels in cultured astrocytes from rat spinal cord. NA, the aragonist phenylephrine, and the beta-agonist isoproterenol decreased the TNF-alpha mRNA level, while the alpha(2)-agonist dexmedetomidine increased it. The isoproterenol-induced TNF-alpha mRNA decrease was accompanied by a decrease in ERK phosphorylation. An adenylyl cyclase activator and an ERK inhibitor mimicked these effects. These results indicate that the transcriptional regulation of TNF-alpha by beta-ARs is mediated via cAMP pathways followed by the ERK pathway inhibition. The dexmedetomidine-induced TNF-alpha mRNA increase was accompanied by phosphorylation of JNK and ERK, which was blocked by a JNK inhibitor. Furthermore, the LPS-induced increase in the TNF-alpha mRNA level was accompanied by NF-kappa B nuclear translocation, and both these effects were blocked by phenylephrine. An NF-kappa B inhibitor suppressed the LPS-induced increase in the TNF-alpha mRNA level. These results suggest that alpha(1)-ARs suppress the LPS-induced increase in the TNF-alpha mRNA level via inhibition of NF-kappa B nuclear translocation. Taken together, our study reveals that both alpha- and beta-ARs are involved in the transcriptional regulation of TNF-alpha in astrocytes. (C) 2020 Elsevier Inc. All rights reserved.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0006-291X
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.bbrc.2020.05.011