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

Abstract

AimsGenistein, 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 methodsMH7A cells were stimulated with tumor necrosis factor (TNF)-α and incubated with genistein, and interleukin (IL)-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF)-κB 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.ResultsGenistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside obviously inhibited TNF-α-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-α-induced proinflammatory cytokine production is dependent on AMPK activation.ConclusionThese findings indicate that genistein suppressed TNF-α-induced inflammation by inhibiting the ROS/Akt/NF-κB pathway and promoting AMPK activation in MH7A cells.

Influence of Dietary Soy Phytoestrogens on Cytokine Production and Immunoglobulin in Ovariectomized Rats

“…The mechanisms underlying these effects are not fully understood, and further investigations are needed to explore the detailed molecular mechanism regulated by phytoestrogens. Genistein significantly reduced inflammatory mediators, such as IL-1β, IL-6 and IL-8 production, in TNF-α-activated MH7A cells in vitro [12]. The anti-inflammatory properties of genistein are mediated by the interruption of the ROS/Akt/NF-κB signaling pathway in MH7A cells.…”

“…The anti-inflammatory properties of genistein are mediated by the interruption of the ROS/Akt/NF-κB signaling pathway in MH7A cells. These signaling led to a marked decrease of TNF-α-induced pro-inflammatory cytokine production [12].…”

Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways

“…In our previous study, we found that ROS can mediate the TNF-α-induced inflammation through the Akt-mediated activation of NF-κB in MH7A cells [28]. To determine whether ROS is involved in the antiinflammation effect, we investigated the potential role of ROS.…”

Radiation Countermeasures: Current Status

“…Hematopoietic cells are recovered due to enhanced activity of IL-6 and G-CSF level and suppression of TNF-α mediated inflammation through inhibition of ROS/Akt/NF-κB pathway by administration of genistein 24 h prior to radiation exposure. Nanoparticle formulation of genistein shows protection from apoptosis in hematopoietic stem and progenitor cells against radiation and increased bone marrow cellularity that promotes hematopoiesis 32,33 .…”