Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts
Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts
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DOI：
10.1093/abbs/gmr027
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发表时间：
2011-05-01
影响因子：
3.7
通讯作者：
Yao, Hangping
中科院分区：
文献类型：
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作者：
Li, Jie;Shao, Xueting;Yao, Hangping
在这项研究中，我们研究和厚朴酚在肿瘤坏死因子α刺激的类风湿性关节炎滑膜成纤维细胞(RASF)中的抗炎作用机制。用和厚朴酚(0~20mU M)预处理的RASF用肿瘤坏死因子-α(20 ng/ml)刺激。采用酶联免疫吸附试验(ELISA)和Griess法检测培养上清液中前列腺素E2(PGE2)、一氧化氮(NO)、可溶性细胞间黏附分子-1(sICAM-1)、转化生长因子-β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)和巨噬细胞炎性蛋白-1α(MIP-1α)水平。免疫印迹法检测环氧合酶-2(COX-2)、诱导型一氧化氮合酶(INOS)、磷酸化Akt、核因子-kappaB(NF-kappa B)和细胞外信号调节蛋白激酶(ERK)1/2的蛋白表达水平。免疫细胞化学方法检测核因子kappaB-p65的表达。经TNF-α处理后，RASF培养上清液中PGE2、NO、sICAM-1、TGF-β1、MCP-1和MIP-1α水平显著上调，COX-2、iNOS蛋白表达增加，Akt、I-kappa B-α、NF-kappa B和ERK1/2蛋白磷酸化。和厚朴酚可剂量依赖性地抑制肿瘤坏死因子-α诱导的这些分子的表达。免疫细胞化学分析证实和厚朴酚对核因子-kappaB-p65活性的抑制作用。综上所述，和厚朴酚是一种潜在的抑制肿瘤坏死因子-α诱导的炎症因子表达的药物，有望成为一种潜在的抗炎药物。
In this study, we investigated the mechanisms underlying the anti-inflammatory effects of honokiol in tumor necrosis factor (TNF)-alpha-stimulated rheumatoid arthritis synovial fibroblasts (RASFs). RASFs pre-treated with honokiol (0-20 mu M) were stimulated with TNF-alpha (20 ng/ml). The levels of prostaglandin E2 (PGE2), nitric oxide (NO), soluble intercellular adhesion molecule- 1 (sICAM-1), transforming growth factor-beta 1 (TGF-beta 1), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in supernatants were determined by enzyme-linked immunosorbent assay (ELISA) and Griess assay. In addition, protein expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated Akt, nuclear factor kappa B (NF kappa B), and extracellular signal-regulated kinase (ERK) 1/2 were determined by western blot. The expression of NF kappa B-p65 was assessed by immunocytochemical analysis. TNF-alpha treatment significantly up-regulated the levels of PGE2, NO, sICAM-1, TGF-beta 1, MCP-1, and MIP-1 alpha in the supernatants of RASFs, increased the protein expression of COX-2, iNOS, and induced phosphorylation of Akt, I kappa B-alpha, NF kappa B, and ERK1/2 in RASFs. TNF-alpha-induced expression of these molecules was inhibited in a dose-dependent manner by pre-treatment with honokiol. The inhibitory effect of honokiol on NF kappa B-p65 activity was also confirmed by immunocytochemical analysis. In conclusion, honokiol is a potential inhibitor of TNF-alpha-induced expression of inflammatory factors in RASFs, which holds promise as a potential anti-inflammatory drug.