Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia

Kao, Tsung-Kuei; Ou, Yen‐Chuan; Lin, Shih‐Yi; Pan, Hung-Chuan; Song, Pei-Jyuan; Raung, Shue-Ling; Lai, Ching-Yi; Liao, Su‐Lan; Lu, Hsi-Chi; Chen, Chun‐Jung

doi:10.1016/j.jnutbio.2010.01.011

Cited by 79 publications

(67 citation statements)

References 60 publications

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“…Not only did the flavonoids inhibit NT-stimulated microglial responses but they also inhibited LPS-stimulated proinflammatory cytokine and chemokine synthesis in microglia, as previously shown in murine microglia (48,70). Greater concentrations of flavonoids are required to inhibit cytokine or chemokine protein release, compared with gene expression.…”

Section: Discussionsupporting

confidence: 67%

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Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism

Patel

Tsilioni

Leeman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

104

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We had reported elevated serum levels of the peptide neurotensin (NT) in children with autism spectrum disorders (ASD). Here, we show that NT stimulates primary human microglia, the resident immune cells of the brain, and the immortalized cell line of human microglia-SV40. NT (10 nM) increases the gene expression and release (P < 0.001) of the proinflammatory cytokine IL-1β and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 from human microglia. NT also stimulates proliferation (P < 0.05) of microglia-SV40. Microglia express only the receptor 3 (NTR3)/sortilin and not the NTR1 or NTR2. The use of siRNA to target sortilin reduces (P < 0.001) the NT-stimulated cytokine and chemokine gene expression and release from human microglia. Stimulation with NT (10 nM) increases the gene expression of sortilin (P < 0.0001) and causes the receptor to be translocated from the cytoplasm to the cell surface, and to be secreted extracellularly. Our findings also show increased levels of sortilin (P < 0.0001) in the serum from children with ASD (n = 36), compared with healthy controls (n = 20). NT stimulation of microglia-SV40 causes activation of the mammalian target of rapamycin (mTOR) signaling kinase, as shown by phosphorylation of its substrates and inhibition of these responses by drugs that prevent mTOR activation. NT-stimulated responses are inhibited by the flavonoid methoxyluteolin (0.1–1 μM). The data provide a link between sortilin and the pathological findings of microglia and inflammation of the brain in ASD. Thus, inhibition of this pathway using methoxyluteolin could provide an effective treatment of ASD.

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Section: Discussionsupporting

confidence: 67%

“…The natural flavonoid luteolin has potent antioxidant and antiinflammatory properties (46). It also inhibits activation of microglia (17,(47)(48)(49). Luteolin also reverses autism-like behavior in mice (50).…”

mentioning

confidence: 99%

Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism

Patel

Tsilioni

Leeman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

107

104

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“…The engagement of HMGB1 and its receptor TLR4 triggers an intracellular signaling cascade resulting in altered gene expression and cell activation. The activation of the HMGB1/TLR4 axis and its downstream effectors Akt and ERK has been implicated in the pathogenesis of cerebral ischemia, expression of pro-inflammatory cytokines, and activation of neutrophils [5,6,22,23]. Thus, our findings suggest that the attenuation of neutrophil activation and iNOS/NO expression by TMP could be a result of inhibition of Akt and ERK activities.…”

Section: Discussionmentioning

confidence: 54%

“…2AeD). These changes of neutrophil activities were paralleled by upregulation of several intracellular regulatory molecules [4e6, 19,22], including Akt phosphorylation (p < 0.01, Fig. 2D), ERK phosphorylation (p < 0.05, Fig.…”

Section: Tmp Reduces Ischemia-induced Activation Of Circulating Neutrmentioning

confidence: 95%

Tetramethylpyrazine inhibits neutrophil activation following permanent cerebral ischemia in rats

Chang

Kao

Chen

et al. 2015

Biochemical and Biophysical Research Communications

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“…They serve as the first line of defense in the brain to protect the CNS from insults. Upon stimulation or neuronal injury, microglia are rapidly activated in response to several pathological pathways, including lipopolysaccharide (LPS), amyloid protein, and interferon-g (IFN-g) (9,10). Notably, microglia exposed to these stimulated factors show altered morphologies and phenotypes and release neuroinflammatory molecules such as nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-a (TNF-a), and interleukin (IL)-1b, all of which contribute to neuronal dysfunction and cell death in a vicious cycle (11,12).…”

Section: Introductionmentioning

confidence: 99%

Xanthoceraside Inhibits Pro-inflammatory Cytokine Expression in Aβ25–35/IFN-γ–Stimulated Microglia Through the TLR2 Receptor, MyD88, Nuclear Factor-κB, and Mitogen-Activated Protein Kinase Signaling Pathways

Zou

Wang

et al. 2013

J Pharmacol Sci

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Abstract. An accumulating body of evidence suggests that Alzheimer's disease (AD) is associated with microglia-mediated neuroinflammation and pro-inflammatory cytokine expression. Therefore, the suppression of neuroinflammation and pro-inflammatory cytokine might theoretically slow down the progression of AD. Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has potent anti-inflammatory and neuroprotective effects. However, the molecular mechanism underlying its anti-inflammatory action remains unclear. In the present study, we attempted to determine the effects of xanthoceraside on the production of pro-inflammatory mediators in amyloid b [25][26][27][28][29][30][31][32][33][34][35] ) / interferon-g (IFN-g)-stimulated microglia. Our results indicated that xanthoceraside (0.01 and 0.1 mM) significantly inhibited the release of nitric oxide (NO) and pro-inflammatory cytokines interleukin-1b and tumor necrosis factor-a in a concentration-dependent manner. Reverse transcriptase-polymerase chain reaction and western blotting analyses showed that xanthoceraside decreased the Ab 25-35 /IFN-ginduced production of cyclooxygenase-2 and inducible NO synthase. These effects were accompanied by inhibited activities of nuclear factor-kB and mitogen-activated protein kinase through Toll-like receptor 2 in a myeloid differentiation protein 88-dependent manner. Our results provide support for the therapeutic potential of xanthoceraside in AD.

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Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia

Cited by 79 publications

References 60 publications

Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism

Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism

Tetramethylpyrazine inhibits neutrophil activation following permanent cerebral ischemia in rats

Xanthoceraside Inhibits Pro-inflammatory Cytokine Expression in Aβ25–35/IFN-γ–Stimulated Microglia Through the TLR2 Receptor, MyD88, Nuclear Factor-κB, and Mitogen-Activated Protein Kinase Signaling Pathways

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