Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages
Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages
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DOI：
10.1016/j.joca.2007.07.009
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发表时间：
2007-11-01
影响因子：
7
通讯作者：
Frondoza, C. G.
中科院分区：
文献类型：
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作者：
Au, R. Y.;Al-Talib, T. K.;Frondoza, C. G.
目的：探讨牛油果大豆不皂化物（ASU）对软骨细胞和单核/巨噬细胞样细胞促炎介质的影响。设计：为了确定ASU的剂量反应，将软骨细胞（5 × 10(5)个细胞/孔）与(1)单独的对照培养基或(2)浓度为0.3、0.9、2.7、8.3和25 μ g/ml的ASU在5% CO2、37℃下孵育72小时。用20 ng/ml脂多糖（LPS）活化细胞24 h，分析细胞上清中前列腺素E-2 （PGE(2)）和亚硝酸盐的含量。软骨细胞和THP-1单核细胞/巨噬细胞（5 × 105个细胞/孔）在5% CO2, 37℃下用(1)单独对照培养基或(2)ASU （25 μ g/ml）孵育72小时。其中一组细胞用LPS （20 ng/ml）激活1 h，进行肿瘤坏死因子- α (tnf - α)、白细胞介素-1 - β (IL-1 β)、环氧化酶-2 （COX-2）和诱导型一氧化氮合酶（NOS）表达的逆转录酶PCR和实时PCR分析。其中一组细胞活化24 h，分析细胞上清液中分泌的PGE2和亚硝酸盐水平。结果：ASU将lps激活的软骨细胞中tnf - α、IL-1 β、COX-2和NOS的表达降低至与未激活的对照组相似的水平。抑制COX-2和NOS表达的同时，细胞上清液中PGE(2)和亚硝酸盐的含量也显著降低。ASU还降低了lps激活的单核细胞/巨噬细胞样细胞中TNF-a和IL-1的表达。结论：本研究表明，ASU的抗炎活性不仅限于软骨细胞，还可以影响单核细胞/巨噬细胞样细胞，这些细胞是滑膜巨噬细胞的原型。这些观察结果为在骨关节炎患者中观察到的ASU减轻疼痛和抗炎作用提供了科学依据。(c) 2007年国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: To evaluate the effects of avocado soybean unsaponifiables (ASU) on proinflammatory mediators in chondrocytes and monocyte/ macrophage-like cells. Design: To determine the dose response of ASU, chondrocytes (5 x 10(5) cells/well) were incubated at 5% CO2, 37 degrees C for 72 h with (1) control media alone or (2) ASU at concentrations of 0.3, 0.9, 2.7, 8.3, and 25 mu g/ml. Cells were activated with 20 ng/ml lipopolysaccharide (LPS) for 24 h and cell supernatants were analyzed for prostaglandin E-2 (PGE(2)) and nitrite content. Chondrocytes and THP-1 monocyte/macrophages (5 x 105 cells/well) were incubated at 5% CO2, 37 degrees C for 72 h with (1) control media alone or (2) ASU (25 mu g/ml). One set of cells was activated for I h with LPS (20 ng/ml) for both reverse-transcriptase PCR and real-time PCR analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 -beta (IL-1 beta), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (NOS) expression. One set of cells was activated for 24 h to analyze secreted PGE2 and nitrite levels in the cellular supernatant. Results: ASU reduced TNF-alpha, IL-1 beta, COX-2, and NOS expression in LPS-activated chondrocytes to levels similar to nonactivated control levels. The suppression of COX-2 and NOS expression was paralleled by a significant reduction in PGE(2) and nitrite, respectively, in the cellular supernatant. ASU also reduced TNF-a and IL-1 expression in LPS-activated monocyte/macrophage-like cells. Conclusion: The present study demonstrates that the anti-inflammatory activity of ASU is not restricted to chondrocytes, but also affects monocyte/macrophage-like cells that serve as a prototype for macrophages in the synovial membrane. These observations provide a scientific rationale for the pain-reducing and anti-inflammatory effects of ASU observed in osteoarthritis patients. (c) 2007 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.