Matches in SemOpenAlex for { <https://semopenalex.org/work/W2800284423> ?p ?o ?g. }
- W2800284423 endingPage "97" @default.
- W2800284423 startingPage "87" @default.
- W2800284423 abstract "Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFNγ) activated BV-2 microglial cells were treated with TQ (12.5 μM for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFκB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFNγ-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p < 0.001), biliverdin reductase A (15 fold; p < 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p < 0.01), and mitochondrial lon protease (>8 fold; p < 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFκB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in >7 fold down-regulation of several NFκB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (CC motif) ligand 3 (CXCL3), chemokine (CC) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the >10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFNγ-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NFκB pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfurtransferase, glutaredoxin-3, and mitochondrial lon protease) in the activated BV-2 microglial cells. Additionally, our results indicate that TQ treatment decreased the activation of the NFκB signaling pathway, which plays a key role in neuroinflammation. In conclusion, our results demonstrate that TQ treatment reduces the inflammatory response and modulates the expression of specific proteins and genes and hence potentially reduce neuroinflammation and neurodegeneration driven by microglial activation." @default.
- W2800284423 created "2018-05-17" @default.
- W2800284423 creator A5013918894 @default.
- W2800284423 creator A5015486918 @default.
- W2800284423 creator A5020830067 @default.
- W2800284423 creator A5035760747 @default.
- W2800284423 date "2018-07-01" @default.
- W2800284423 modified "2023-10-08" @default.
- W2800284423 title "Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells" @default.
- W2800284423 cites W117392025 @default.
- W2800284423 cites W1263203087 @default.
- W2800284423 cites W137594095 @default.
- W2800284423 cites W1485337864 @default.
- W2800284423 cites W1493890929 @default.
- W2800284423 cites W1505540405 @default.
- W2800284423 cites W1507809553 @default.
- W2800284423 cites W1533236567 @default.
- W2800284423 cites W1542037208 @default.
- W2800284423 cites W1563590122 @default.
- W2800284423 cites W1588635193 @default.
- W2800284423 cites W1613451007 @default.
- W2800284423 cites W1787143736 @default.
- W2800284423 cites W1825991678 @default.
- W2800284423 cites W1861458934 @default.
- W2800284423 cites W187575719 @default.
- W2800284423 cites W1878700164 @default.
- W2800284423 cites W1966582616 @default.
- W2800284423 cites W1967456541 @default.
- W2800284423 cites W1967990977 @default.
- W2800284423 cites W1968323285 @default.
- W2800284423 cites W1968362444 @default.
- W2800284423 cites W1970127176 @default.
- W2800284423 cites W1974305753 @default.
- W2800284423 cites W1976306764 @default.
- W2800284423 cites W1976312989 @default.
- W2800284423 cites W1976549710 @default.
- W2800284423 cites W1980543900 @default.
- W2800284423 cites W1981705617 @default.
- W2800284423 cites W1982190619 @default.
- W2800284423 cites W1983368219 @default.
- W2800284423 cites W1986384924 @default.
- W2800284423 cites W1987703244 @default.
- W2800284423 cites W1987777210 @default.
- W2800284423 cites W1988631382 @default.
- W2800284423 cites W1989981838 @default.
- W2800284423 cites W1991599211 @default.
- W2800284423 cites W1996024251 @default.
- W2800284423 cites W1999088334 @default.
- W2800284423 cites W1999392081 @default.
- W2800284423 cites W2000393531 @default.
- W2800284423 cites W2002794726 @default.
- W2800284423 cites W2003674452 @default.
- W2800284423 cites W2004349171 @default.
- W2800284423 cites W2005044790 @default.
- W2800284423 cites W2007197518 @default.
- W2800284423 cites W2011361113 @default.
- W2800284423 cites W2013741750 @default.
- W2800284423 cites W2014788740 @default.
- W2800284423 cites W2016232584 @default.
- W2800284423 cites W2016901103 @default.
- W2800284423 cites W2020788984 @default.
- W2800284423 cites W2020864781 @default.
- W2800284423 cites W2021443072 @default.
- W2800284423 cites W2022690437 @default.
- W2800284423 cites W2023136593 @default.
- W2800284423 cites W2026484283 @default.
- W2800284423 cites W2027783468 @default.
- W2800284423 cites W2028558310 @default.
- W2800284423 cites W2030365747 @default.
- W2800284423 cites W2030488845 @default.
- W2800284423 cites W2031969613 @default.
- W2800284423 cites W2034717030 @default.
- W2800284423 cites W2035077601 @default.
- W2800284423 cites W2035158278 @default.
- W2800284423 cites W2036091553 @default.
- W2800284423 cites W2037172408 @default.
- W2800284423 cites W2037203209 @default.
- W2800284423 cites W2039854830 @default.
- W2800284423 cites W2044313353 @default.
- W2800284423 cites W2048378844 @default.
- W2800284423 cites W2050327248 @default.
- W2800284423 cites W2051504363 @default.
- W2800284423 cites W2052250375 @default.
- W2800284423 cites W2053753642 @default.
- W2800284423 cites W2056311398 @default.
- W2800284423 cites W2056743214 @default.
- W2800284423 cites W2057495929 @default.
- W2800284423 cites W2059700478 @default.
- W2800284423 cites W2063207603 @default.
- W2800284423 cites W2063249182 @default.
- W2800284423 cites W2063576478 @default.
- W2800284423 cites W2063858768 @default.
- W2800284423 cites W2064711537 @default.
- W2800284423 cites W2069134915 @default.
- W2800284423 cites W2070576387 @default.
- W2800284423 cites W2073181814 @default.
- W2800284423 cites W2073803664 @default.
- W2800284423 cites W2075308841 @default.