Effects of hypnotic bromovalerylurea on microglial BV2 cells
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocatio...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861317300816 |
| _version_ | 1819095151874670592 |
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| author | Shun Kawasaki Naoki Abe Fumito Ohtake Afsana Islam Mohammed Emamussalehin Choudhury Ryo Utsunomiya Satoshi Kikuchi Tasuku Nishihara Jun Kuwabara Hajime Yano Yuji Watanabe Mayuki Aibiki Toshihiro Yorozuya Junya Tanaka |
| author_facet | Shun Kawasaki Naoki Abe Fumito Ohtake Afsana Islam Mohammed Emamussalehin Choudhury Ryo Utsunomiya Satoshi Kikuchi Tasuku Nishihara Jun Kuwabara Hajime Yano Yuji Watanabe Mayuki Aibiki Toshihiro Yorozuya Junya Tanaka |
| author_sort | Shun Kawasaki |
| collection | DOAJ |
| description | An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level. |
| first_indexed | 2024-12-21T23:38:45Z |
| format | Article |
| id | doaj.art-c8463556dad744698cc99499ed5c67c5 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-21T23:38:45Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-c8463556dad744698cc99499ed5c67c52022-12-21T18:46:18ZengElsevierJournal of Pharmacological Sciences1347-86132017-06-01134211612310.1016/j.jphs.2017.05.007Effects of hypnotic bromovalerylurea on microglial BV2 cellsShun Kawasaki0Naoki Abe1Fumito Ohtake2Afsana Islam3Mohammed Emamussalehin Choudhury4Ryo Utsunomiya5Satoshi Kikuchi6Tasuku Nishihara7Jun Kuwabara8Hajime Yano9Yuji Watanabe10Mayuki Aibiki11Toshihiro Yorozuya12Junya Tanaka13Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Emergency Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Anesthesiology and Resuscitology, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanDepartment of Gastrointestinal Surgery and Surgical Oncology, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Emergency Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Anesthesiology and Resuscitology, Graduate School of Medicine, Ehime University, Toon, Ehime, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, JapanAn old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level.http://www.sciencedirect.com/science/article/pii/S1347861317300816NOATPMicrogliaMacrophageRotenone |
| spellingShingle | Shun Kawasaki Naoki Abe Fumito Ohtake Afsana Islam Mohammed Emamussalehin Choudhury Ryo Utsunomiya Satoshi Kikuchi Tasuku Nishihara Jun Kuwabara Hajime Yano Yuji Watanabe Mayuki Aibiki Toshihiro Yorozuya Junya Tanaka Effects of hypnotic bromovalerylurea on microglial BV2 cells Journal of Pharmacological Sciences NO ATP Microglia Macrophage Rotenone |
| title | Effects of hypnotic bromovalerylurea on microglial BV2 cells |
| title_full | Effects of hypnotic bromovalerylurea on microglial BV2 cells |
| title_fullStr | Effects of hypnotic bromovalerylurea on microglial BV2 cells |
| title_full_unstemmed | Effects of hypnotic bromovalerylurea on microglial BV2 cells |
| title_short | Effects of hypnotic bromovalerylurea on microglial BV2 cells |
| title_sort | effects of hypnotic bromovalerylurea on microglial bv2 cells |
| topic | NO ATP Microglia Macrophage Rotenone |
| url | http://www.sciencedirect.com/science/article/pii/S1347861317300816 |
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