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Bidirectional modulation of TNF-alpha transcription via alpha- and beta-adrenoceptors in cultured astrocytes from rat spinal cord
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| Title: | Bidirectional modulation of TNF-alpha transcription via alpha- and beta-adrenoceptors in cultured astrocytes from rat spinal cord |
| Authors: | Morimoto, Kohei Browse this author | | Kitano, Taisuke Browse this author | | Eguchi, Ryota Browse this author →KAKEN DB | | Otsuguro, Ken-ichi Browse this author →KAKEN DB |
| Keywords: | Astrocyte | | Noradrenaline | | Adrenoceptors | | TNF-alpha | | Transcription factor |
| Issue Date: | 12-Jul-2020 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 528 |
| Issue: | 1 |
| Start Page: | 78 |
| End Page: | 84 |
| Publisher DOI: | 10.1016/j.bbrc.2020.05.011 |
| Abstract: | 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. |
| Rights: | © 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/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82212 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 乙黒 兼一
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