| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Stimulation of nuclear receptor REV-ERBs suppresses production of pronociceptive molecules in cultured spinal astrocytes and ameliorates mechanical hypersensitivity of inflammatory and neuropathic pain of mice |
|
言語 |
en |
| 作成者 |
Morioka, Norimitsu
Kodama, Keitaro
Tomori, Mizuki
Yoshikawa, Kanade
Saeki, Munenori
Nakamura, Yoki
Zhang, Fang Fang
Hisaoka-Nakashima, Kazue
Nakata, Yoshihiro
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 権利情報 |
|
|
権利情報 |
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認、ご利用ください。 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
REV-ERBs |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Chronic pain |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Astrocyte |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Spinal dorsal horn |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Interleukin-1β |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Interleukin-6 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Tumor necrosis factor |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
siRNA |
| 内容記述 |
|
|
内容記述 |
The orphan nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammatory-related gene transcription in astroglioma cells, but their role in nociceptive transduction has yet to be elaborated. Spinal dorsal horn astrocytes contribute to the maintenance of chronic pain. Treatment of cultured spinal astrocytes with specific REV-ERBs agonists SR9009 or GSK4112 significantly prevented lipopolysaccharide (LPS)-induced mRNA upregulation of pronociceptive molecules interleukin-1β (IL-1β) mRNA, interleukin-6 (IL-6) mRNA and matrix metalloprotease-9 (MMP-9) mRNA, but not CCL2 mRNA expression. Treatment with SR9009 also blocked tumor necrosis factor-induced IL-1β mRNA, IL-6 mRNA and MMP-9 mRNA. In addition, treatment with SR9009 significantly blocked LPS-induced upregulation of IL-1β protein, IL-6 protein and MMP-9 activity. The inhibitory effects of SR9009 on LPS-induced expression of pronociceptive molecules were blocked by knockdown of REV-ERBs expression with short interference RNA, confirming that SR9009 exerts its effect through REV-ERBs. Intrathecal LPS treatment in male mice induces hind paw mechanical hypersensitivity, and upregulation of IL-1β mRNA, IL-6 mRNA and glial fibrillary acidic protein (GFAP) expression in spinal dorsal horn. Intrathecal pretreatment of SR9009 prevented the onset of LPS-induced mechanical hypersensitivity, cytokine expression and GFAP expression. Intrathecal injection of SR9009 also ameliorated mechanical hypersensitivity during the maintenance phase of complete Freund’s adjuvant-induced inflammatory pain and partial sciatic nerve ligation-, paclitaxel-, and streptozotocin-induced neuropathy in mice. The current findings suggest that spinal astrocytic REV-ERBs could be critical in the regulation of nociceptive transduction through downregulation of pronociceptive molecule expression. Thus, spinal REV-ERBs could be an effective therapeutic target in the treatment of chronic pain. |
|
言語 |
en |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
This work was supported by Grant-in-Aid for Scientific Research (C) grant number 26460342, and grants from the Takeda Science Foundation, Suzuken Memorial Foundation, The Uehara Memorial Foundation and The Nakatomi Foundation. Experiments were carried out using equipment at the Analysis Center of Life Science, Hiroshima University and the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University. |
| 出版者 |
|
|
出版者 |
Elsevier |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AO |
|
出版タイプResource |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1016/j.bbi.2019.01.014 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.bbi.2019.01.014 |
| 関連情報 |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
30682503 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0889-1591 |
| 開始ページ |
|
|
開始ページ |
116 |
| 書誌情報 |
Brain, Behavior, and Immunity
Brain, Behavior, and Immunity
巻 78,
p. 116-130,
発行日 2019-05
|
| 旧ID |
48640 |
| 備考 |
Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months. |
BrainBehavImmun_78_116.pdf (1.1 MB)
