Abstract
BackgroundUpregulation 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.MethodsHerein, 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.ResultsWe 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.ConclusionsThese 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.
Highlights
Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers
Lee et al Journal of Neuroinflammation (2020) 17:177 (Continued from previous page). These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of Protein kinase C (PKC)-δ-dependent reactive oxygen species (ROS)-mediated Matrix metalloproteinases (MMPs)-9 expression in brain astrocytes
We investigate whether the PKC activator, phorbol 12-myristate 13-acetate (PMA), can upregulate MMP-9 expression in rat brain astrocytes (RBA), cells were treated with PMA (1 μM) for the indicated time intervals, and the conditioned media were collected and analyzed
Summary
Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. 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 antiinflammatory activities. The rottlerin is a polyphenol natural product isolated from the Asian Kamala plant Mallotus philippinensis [3] and displays a complex spectrum of pharmacology and an array of medicinal properties. It has been used as a protein kinase C-δ (PKC-δ) inhibitor. The mechanisms of rottlerin in the CNS neuroprotective action remain unclear
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