TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro.
TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro.
复制标题
DOI：
10.1186/ar4085
复制
发表时间：
2012-11-07
影响因子：
4.9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Qin J;Shang L;Ping AS;Li J;Li XJ;Yu H;Magdalou J;Chen LB;Wang H
阿魏酸钠（SF）是中药的天然成分。我们前期的研究表明，SF对骨关节炎（OA）具有保护作用。本研究旨在探讨SF对大鼠OA软骨细胞TNF/TNF受体（TNFR）信号转导通路的影响。用IL-1β和SF共同处理原代大鼠关节软骨细胞。用异硫氰酸荧光素-膜联蛋白V/碘化丙啶法检测软骨细胞凋亡。应用PCR芯片筛选84个凋亡相关基因的表达。ELISA法检测TNFα和前列腺素E2的释放。蛋白质印迹法检测蛋白质表达。电泳迁移率变动分析（EMSA）检测NF-κB活性。实时定量PCR检测诱导型一氧化氮合酶（iNOS）基因表达。用Griess法测定一氧化氮含量。SF处理后软骨细胞凋亡率明显降低（P < 0.01）。凋亡PCR芯片的结果表明，在TNF/TNFR通路中的一些核心蛋白的mRNA表达显示出有价值的调节。SF浓度依赖性地抑制TNFα、TNFR-1、TNF受体相关死亡结构域、caspase-8和caspase-3的蛋白表达。与模型对照组相比，SF对caspase-8、caspase-3活性也有明显的抑制作用（P < 0.01）。TNF受体相关因子-2表达、NF-κB激酶（IKK）α和β亚基抑制剂以及NF-κB抑制剂α（IκBα）的磷酸化均受到SF处理的浓度依赖性抑制。EMSA结果显示SF抑制了NF-κB的活性。SF治疗组COX-2、iNOS的表达及前列腺素E2、NO的含量明显低于对照组（P < 0.01）。SF对IL-1β诱导的OA模型具有抗凋亡和抗炎作用，其机制可能与抑制TNF/TNFR通路中caspase依赖的凋亡通路和IKK/NF-κB信号转导通路有关。
Sodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes. Primary rat articular chondrocytes were co-treated with IL-1β and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNFα and prostaglandin E2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method. After treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNFα, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-κB kinase (IKK) subunits alpha and beta, and NF-κB inhibitor, alpha (IκBα) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-κB. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were attenuated with the treatment of SF (P < 0.01). SF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1β in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-κB signal transduction pathway of the TNF/TNFR pathway.
登录
查看更多内容
影响因子：
3.7
作者：
Liacini, A;Sylvester, J;Zafarullah, M
通讯作者：
Zafarullah, M
影响因子：
2.8
作者：
Aizawa, T;Kon, T;Gerstenfeld, LC
通讯作者：
Gerstenfeld, LC
DOI：
10.1089/jir.2008.0076
发表时间：
2009-05
期刊：
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
影响因子：
--
作者：
Saperstein S;Chen L;Oakes D;Pryhuber G;Finkelstein J
通讯作者：
Finkelstein J
影响因子：
--
作者：
El Mansouri, Fatima Ezzahra;Chabane, Nadir;Fahmi, Hassan
通讯作者：
Fahmi, Hassan
DOI：
10.1016/j.bbagen.2005.12.017
发表时间：
2006-02-01
影响因子：
3
作者：
Khanduja, KL;Avti, PK;Pathak, CM
通讯作者：
Pathak, CM