Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal
Abstract Background Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01859-5 |
| _version_ | 1818340647976828928 |
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| author | Tsong-Hai Lee Jiun-Liang Chen Pei-Shan Liu Ming-Ming Tsai Su-Jane Wang Hsi-Lung Hsieh |
| author_facet | Tsong-Hai Lee Jiun-Liang Chen Pei-Shan Liu Ming-Ming Tsai Su-Jane Wang Hsi-Lung Hsieh |
| author_sort | Tsong-Hai Lee |
| collection | DOAJ |
| description | Abstract Background Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegeneration. In addition, protein kinase Cs (PKCs) has been shown to be involved in regulation of various inflammatory factors like MMP-9 by several stimuli in many cell types. Several phytochemicals are believed to reduce the risk of several inflammatory disorders including the CNS diseases. The rottlerin, a principal phenolic compound of the Kamala plant Mallotus philippinensis, has been shown to possess an array of medicinal properties, including anti-PKC-δ, antitumor, anti-oxidative, and anti-inflammatory activities. Methods Herein, we used rat brain astrocytes (RBA) to demonstrate the signaling mechanisms of phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression by zymographic, RT-PCR, subcellular isolation, Western blot, ROS detection, and promoter reporter analyses. Then, we evaluate the effects of rottlerin on PMA-induced MMP-9 expression in RBA and its influencing mechanism. Results We first demonstrated that PMA stimulated activation of various types of PKC, including PKC-δ in RBA. Subsequently, PMA induced MMP-9 expression via PKCδ-mediated reactive oxygen species (ROS) generation, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, and then induced c-Fos/AP-1 signaling pathway. Finally, upregulation of MMP-9 by PMA via the pathway may promote astrocytic migration, and the event could be attenuated by rottlerin. Conclusions These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of PKC-δ-dependent ROS-mediated MMP-9 expression in brain astrocytes. |
| first_indexed | 2024-12-13T15:46:14Z |
| format | Article |
| id | doaj.art-8c2f87c6291941a7bfb19306457c5298 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T15:46:14Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-8c2f87c6291941a7bfb19306457c52982022-12-21T23:39:42ZengBMCJournal of Neuroinflammation1742-20942020-06-0117111310.1186/s12974-020-01859-5Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signalTsong-Hai Lee0Jiun-Liang Chen1Pei-Shan Liu2Ming-Ming Tsai3Su-Jane Wang4Hsi-Lung Hsieh5Stroke Center and Stroke Section, Department of Neurology, College of Medicine, Chang Gung Memorial Hospital, Linkou Medical Center and Chang Gung UniversityDivision of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, College of Medicine, Chang Gung UniversityDepartment of Microbiology, Soochow UniversityDepartment of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and TechnologySchool of Medicine, Fu Jen Catholic UniversityDepartment of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and TechnologyAbstract Background Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegeneration. In addition, protein kinase Cs (PKCs) has been shown to be involved in regulation of various inflammatory factors like MMP-9 by several stimuli in many cell types. Several phytochemicals are believed to reduce the risk of several inflammatory disorders including the CNS diseases. The rottlerin, a principal phenolic compound of the Kamala plant Mallotus philippinensis, has been shown to possess an array of medicinal properties, including anti-PKC-δ, antitumor, anti-oxidative, and anti-inflammatory activities. Methods Herein, we used rat brain astrocytes (RBA) to demonstrate the signaling mechanisms of phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression by zymographic, RT-PCR, subcellular isolation, Western blot, ROS detection, and promoter reporter analyses. Then, we evaluate the effects of rottlerin on PMA-induced MMP-9 expression in RBA and its influencing mechanism. Results We first demonstrated that PMA stimulated activation of various types of PKC, including PKC-δ in RBA. Subsequently, PMA induced MMP-9 expression via PKCδ-mediated reactive oxygen species (ROS) generation, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, and then induced c-Fos/AP-1 signaling pathway. Finally, upregulation of MMP-9 by PMA via the pathway may promote astrocytic migration, and the event could be attenuated by rottlerin. Conclusions These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of PKC-δ-dependent ROS-mediated MMP-9 expression in brain astrocytes.http://link.springer.com/article/10.1186/s12974-020-01859-5RottlerinMatrix metalloproteinase-9Protein kinase C-δReactive oxygen speciesBrain astrocytesNeuroinflammation |
| spellingShingle | Tsong-Hai Lee Jiun-Liang Chen Pei-Shan Liu Ming-Ming Tsai Su-Jane Wang Hsi-Lung Hsieh Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal Journal of Neuroinflammation Rottlerin Matrix metalloproteinase-9 Protein kinase C-δ Reactive oxygen species Brain astrocytes Neuroinflammation |
| title | Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal |
| title_full | Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal |
| title_fullStr | Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal |
| title_full_unstemmed | Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal |
| title_short | Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal |
| title_sort | rottlerin a natural polyphenol compound inhibits upregulation of matrix metalloproteinase 9 and brain astrocytic migration by reducing pkc δ dependent ros signal |
| topic | Rottlerin Matrix metalloproteinase-9 Protein kinase C-δ Reactive oxygen species Brain astrocytes Neuroinflammation |
| url | http://link.springer.com/article/10.1186/s12974-020-01859-5 |
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