دورية أكاديمية
DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1β-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells
| العنوان: | DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1β-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells |
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| المؤلفون: | Takuya Kusakabe, Yasunobu Sawaji, Kenji Endo, Hidekazu Suzuki, Takamitsu Konishi, Asato Maekawa, Kazuma Murata, Kengo Yamamoto |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 1, p 371 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | dual-specificity phosphatase (DUSP)-1, prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), interleukin-1β (IL-1β), mitogen-activated protein kinase (MAPK), nerve growth factor (NGF), Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1β (IL-1β). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1β is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1β-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1β-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1β-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1β-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 23010371 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/23/1/371; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms23010371 |
| URL الوصول: | https://doaj.org/article/950690eeb1e6480489956b81ba012dfd |
| رقم الأكسشن: | edsdoj.950690eeb1e6480489956b81ba012dfd |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23010371 14220067 16616596 |
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| DOI: | 10.3390/ijms23010371 |