[TAK基因沉默对肿瘤坏死因子-α诱导的成纤维样滑膜细胞中白细胞介素-6和白细胞介素-8表达的影响]
[Effects of TAK gene silencing on the expressions of IL-6 and IL-8 induced by TNF-α in fibroblast-like synoviocytes].
作者信息
Mo Xuan-Rong, Xie Jiang-Wen, Lv Guo-Ju, Ke Yu-Ping, Luo Xin-Jing
机构信息
Department of Basic Medical Sciences, School of Medicine of Taizhou University, Taizhou 318000.
Department of Cardiology, Yingzhou District Second people's Hospital, Ningbo 315000, China.
出版信息
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2017 May 8;33(5):471-475. doi: 10.12047/j.cjap.5494.2017.113.
OBJECTIVE
To investigate the effects of silencing transforming growth factor-β activating kinase 1 (TAK1)on the expressions of IL-6 and IL-8 induced by TNF-α in fibroblast-like synoviocytes, and to explore the role of TAK1 in rheumatoid arthritis (RA).
METHODS
The synthesized TAK1 siRNA and scrambled siRNA (ScRNA) were transferred into cultured RA fibroblast-like synoviocyte line MH7A by lipofectamine. The expressions of the pro-inflammatory mediator IL-6 and IL-8 and the levels of phospho-P38(p-P38), phospho-C-Jun NH2-terminal kinase(p-JNK), phospho-extracellular signal-regulated kinase(p-ERK), phospho-p65(p-p65) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha(IκBa) were examined.
RESULTS
Silencing of TAK was demonstrated in synoviocytes transfected by TAK siRNA. TAK1 silencing markedly attenuated the expression of IL-6 and IL-8 in the presence of TNF-α. TAK1 silencing inhibited the activation of p38 and JNK MAPK. TAK1 silencing also inhibited activation of nuclear factor-κB (NF-κB).
CONCLUSIONS
TAK1 silencing attenuated the expression of IL-6 and IL-8 in synoviocytes induced by TNF-α inhibiting the activation of p38, JNK MAPK and NF-κB.
目的
探讨沉默转化生长因子-β激活激酶1（TAK1）对肿瘤坏死因子-α（TNF-α）诱导的成纤维样滑膜细胞中白细胞介素-6（IL-6）和白细胞介素-8（IL-8）表达的影响，以探究TAK1在类风湿关节炎（RA）中的作用。
方法
通过脂质体将合成的TAK1小干扰RNA（siRNA）和乱序siRNA（ScRNA）转染至培养的RA成纤维样滑膜细胞系MH7A中。检测促炎介质IL-6和IL-8的表达以及磷酸化P38（p-P38）、磷酸化C-Jun氨基末端激酶（p-JNK）、磷酸化细胞外信号调节激酶（p-ERK）、磷酸化p65（p-p65）和B细胞中κ轻链多肽基因增强子的核因子α（IκBa）的水平。
结果
TAK siRNA转染的滑膜细胞中证实了TAK1的沉默。在存在TNF-α的情况下，TAK1沉默显著减弱了IL-6和IL-8的表达。TAK1沉默抑制了p38和JNK丝裂原活化蛋白激酶（MAPK）的激活。TAK1沉默还抑制了核因子-κB（NF-κB）的激活。
结论
TAK1沉默减弱了TNF-α诱导的滑膜细胞中IL-6和IL-8的表达，抑制了p38、JNK MAPK和NF-κB的激活。
Zotero 插件