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Genistein attenuates pro‐inflammatory pathways in human brain microvascular endothelial cells

Pro‐inflammatory cerebromicrovascular environment has been implicated in the critical early pathologic events in a variety of neurodegenerative diseases. Recent studies also have demonstrated the potential beneficial effects of soy isoflavones. However, cellular and molecular mechanisms underlying this process remain unclear. The present study was designed to examine the hypothesis that soy isoflavone genistein may attenuate cytokine‐induced pro‐inflammatory pathways in human brain microvascular endothelial cells (HBMEC). The quantitative real‐time RT‐PCR and ELISA showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose‐dependently inhibited cytokine‐induced up‐regulation of mRNA and protein expression of pro‐inflammatory mediators such as cytokines (IL‐1δ and TNF‐α), chemokines (MCP‐1 and IL‐8), and adhesion molecule (ICAM‐1). Genistein also markedly blocked the activation of transcription factor STAT1 in HBMEC exposed to cytokine as measured by electrophoretic mobility shift assay (EMSA). In addition, genistein pretreatment significantly inhibited transmigration of blood leukocytes across HBMEC monolayer stimulated by cytokine in a dose‐dependent manner. Our results suggest that genistein may protect against cytokine‐induced overexpression of pro‐inflammatory mediators and inflammatory reactions in human brain microvascular endothelium via blocking the transcription factor(s)‐mediated molecular signaling pathways