基础医学与临床 ›› 2015, Vol. 35 ›› Issue (8): 1089-1093.

• 研究论文 • 上一篇    下一篇

IL-1β诱导内质网应激增加人软骨细胞凋亡及初步机制

史达,赵聪喆,柴惠斌,李喆,韩为华,孙银娣   

  1. 西安交通大学医学院附属红会医院
  • 收稿日期:2014-11-17 修回日期:2015-03-26 出版日期:2015-08-05 发布日期:2015-07-15
  • 通讯作者: 史达 E-mail:983595466@qq.com

IL-1β induced endoplasmic reticulum stress increases human chondrocyte apoptosis and the mechanism

  • Received:2014-11-17 Revised:2015-03-26 Online:2015-08-05 Published:2015-07-15

摘要: 目的 分析炎性因子(IL-1β与TNF-α)对内质网应激(ERS)的影响以及与骨关节软骨细胞凋亡的关系,探讨相关分子机制。方法 收集正常与OA患者骨关?节软骨组织各20例,RT-PCR法检测软骨组织中炎症因子IL-1β、TNF-α及ERS相关因子GRP78、CHOP的mRNA水平。Western blot法检测体外培养软骨细胞中GRP78、CHOP、ATF4和caspase-3表达,TUNEL法检测细胞凋亡。结果 与对照组相比,OA患者骨关节软骨组织中IL-1β、TNF-α与GRP78、CHOP的mRNA表达水平均显著上调(P<0.01),IL-1β与GRP78、CHOP的高表达呈显著正相关(P<0.05)。体外实验表明,IL-1β(2 ng/L)作用下,软骨细胞GRP78、CHOP、ATF4表达水平及细胞凋亡水平较对照组均显著增高(P<0.01);TNF-α作用下,GRP78、caspase-3表达水平及细胞凋亡水平较对照组显著上调(P<0.01)。结论 2 ng/L及更高浓度的IL-1β可激活ATF4-CHOP介导的ERS反应而诱导软骨细胞凋亡。

关键词: 骨关节炎, IL-1β, CHOP, 质网应激, 细胞凋亡

Abstract: Objective To analysis the effects of inflammation factors (IL-1β, TNF-α) on endoplasmic reticulum stress (ERS) and the association with osteoarticular chondrocyte apoptosis. Methods Osteoarticular cartilage tissues were collected from normal and patients with OA (20 cases for each group). RT-PCR were performed to measure the mRNA level of IL-1β, TNF-α, GRP78 and CHOP in cartilaginous tissues. Western blot was used to evaluate the expression of GRP78, CHOP, ATF4 and caspase-3 in chondrocytes. The apoptosis of chondrocyte was analyzed by TUNEL. Results Compared with control, mRNA levels of IL-1β, TNF-α, GRP78 and CHOP in OA were significantly higher (P<0.01), while the high expression of IL-1β was positively correlated to GRP78 and CHOP (P<0.05). In vitro, GRP78, CHOP, ATF4 expression and chondrocyte apoptosis significantly increased in response to the treatment of IL-1β (2 ng/L) (P<0.01). In addition, the expression of GRP78, caspase-3 and chondrocyte apoptosis were significantly higher after incubation with TNF-α (P<0.01). Conclusion 2 ng/L and higher dosage of IL-1β triggered ATF4-CHOP-mediated ERS to induce chondrocyte apoptosis.

Key words: Osteoarthritis, IL-1β, CHOP, ER stress, cell apoptosis