Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.
Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Buraket al.
[en] Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Eren, Erden; Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
Tufekci, Kemal Ugur; Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
Isci, Kamer Burak; Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
Genc, Kursad; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
Genc, Sermin; Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylül University, Izmir, Turkey
External co-authors :
yes
Language :
English
Title :
Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.
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