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首页> 外文期刊>Life sciences >Downregulation of nuclear factor-kappa B (NF-kappaB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis.
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Downregulation of nuclear factor-kappa B (NF-kappaB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis.

机译：水飞蓟宾在巴西副球菌攻击的人单核细胞中下调核因子-κB（NF-κB）通路。

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摘要

AIMS: Silibinin is the major active component of silymarin, a polyphenolic plant flavonoid that has anti-inflammatory effects. The modulatory effect of silibinin on monocyte function against Paracoccidioides brasiliensis (Pb18) has not yet been demonstrated. The present study investigated whether the effect of silibinin on nuclear factor-kappa B (NF-kappaB) pathways may affect the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1), prostaglandin E(2) (PGE(2)), nitric oxide (NO) and fungicidal activity of human monocytes challenged in vitro with Pb18. MAIN METHODS: Peripheral blood monocytes from healthy individuals were treated with silibinin and challenged with Pb18 for 18h. TNF-alpha, IL-10, TGF-beta1 and PGE(2) expression were determined by immunoenzymatic assay (ELISA) and NO release was determined by the accumulation of nitrite in culture supernatants. Fungicidal activity of monocytes was analyzed after treatment with interferon-gamma plus silibinin and challenge with Pb18. NF-kappaB activation in cultured monocytes was evaluated by flow cytometry and ELISA. KEY FINDINGS: Silibinin partially inhibited p65NF-kappaB activation as the number of cells expressing this factor was reduced and the concentration of nuclear p65NF-kappaB was low, compared to untreated controls. The addition of silibinin also resulted in suppression of TNF-alpha, IL-10, TGF-beta1, PGE(2) and NO production but did not affect the fungicidal activity of monocytes against Pb18. SIGNIFICANCE: Silibinin exerts anti-inflammatory and anti-fibrotic effects on CD14+/- human monocytes challenged by Pb18 by partial inhibition of p65NF-kappaB activation.
机译：目的：水飞蓟宾是水飞蓟素的主要活性成分，水飞蓟素是一种具有抗炎作用的多酚类植物类黄酮。尚未证实水​​飞蓟宾对巴西副球菌（Pb18）单核细胞功能的调节作用。本研究调查了水飞蓟宾对核因子-κB（NF-kappaB）通路的影响是否会影响肿瘤坏死因子-α（TNF-alpha），白介素-10（IL-10），转化生长因子β的产生（TGF-beta1），前列腺素E（2）（PGE（2）），一氧化氮（NO）和人类单核细胞在体外受Pb18攻击的杀真菌活性。主要方法：将健康人的外周血单核细胞用水飞蓟宾处理，并用Pb18攻击18h。 TNF-α，IL-10，TGF-beta1和PGE（2）的表达通过免疫酶法（ELISA）确定，NO的释放通过亚硝酸盐在培养上清液中的积累来确定。用干扰素-γ加水飞蓟宾处理并用Pb18攻击后，分析单核细胞的杀真菌活性。通过流式细胞仪和ELISA评估培养的单核细胞中的NF-κB活化。主要发现：与未处理的对照组相比，水飞蓟宾部分抑制了p65NF-kappaB的活化，因为表达该因子的细胞数量减少了，而核p65NF-kappaB的浓度却很低。水飞蓟宾的添加还导致抑制TNF-α，IL-10，TGF-beta1，PGE（2）和NO的产生，但不影响单核细胞对Pb18的杀真菌活性。意义：水飞蓟宾通过部分抑制p65NF-κB的活化，对Pb18攻击的CD14 +/-人单核细胞发挥抗炎和抗纤维化作用。

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