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Genistein suppresses tumor necrosis factor ?-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor ?B and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells.

ABSTRACT: AIMS: Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA). However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression. MATERIALS AND METHODS: MH7A cells were stimulated with tumor necrosis factor (TNF)-? and incubated with genistein, and interleukin (IL)-1?, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF)-?B was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS) was monitored using the fluorescent probe 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot. RESULTS: Genistein decreased the secretion of IL-1?, IL-6, and IL-8 from TNF-?-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-?-induced NF-?B translocation as well as phosphorylation of I?B kinase-?/? and I?B?, and also suppressed TNF-?-induced AMPK inhibition. The production of IL-1?, IL-6, and IL-8 induced by TNF-? was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1?, IL-6, and IL-8 production induced by TNF-?. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside obviously inhibited TNF-?-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-?-induced proinflammatory cytokine production is dependent on AMPK activation. CONCLUSION: These findings indicate that genistein suppressed TNF-?-induced inflammation by inhibiting the ROS/Akt/NF-?B pathway and promoting AMPK activation in MH7A cells.

SUBMITTER: Li J

PROVIDER: S-EPMC3962316 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells.

Li Jinchao J Li Jun J Yue Ye Y Hu Yiping Y Cheng Wenxiang W Liu Ruoxi R Pan Xiaohua X Zhang Peng P

Drug design, development and therapy 20140317

<h4>Aims</h4>Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA). However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression.<h4>Materials and methods</h4>MH7A cells were stimulated with tumor necrosis factor (TNF)-α and incubated with genistein, and ...[more]

PMID: 24669186

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Project description:BackgroundIntestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms.AimThe aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS).Materials and methodsFreshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 μg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane.ResultsCSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly (p<0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation.ConclusionThese data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions.

Dataset Information

Genistein suppresses tumor necrosis factor ?-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor ?B and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells.

Publications

Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells.

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