Kuo Chun-Lin, Liu Shu-Ting, Chang Yung-Lung, Wu Chia-Chun, Huang Shih-Ming
Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, Republic of China.
Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China.
Oncotarget. 2018 Aug 21;9(65):32478-32495. doi: 10.18632/oncotarget.25980.
Interleukin (IL)-11, a member of the IL-6 family of cytokines, exerts pleiotropic effects under normal and various disease conditions. We assessed expression regulation and the IL-11/IL-6 ratio in osteoarthritis (OA) to better guide clinical therapeutic decision-making. Our findings suggest that Zac1, a zinc finger protein that regulates apoptosis and cell cycle arrest, is a transcription factor regulating expression. Zac1 overexpression or knockdown respectively induced or suppressed expression in HeLa cells. Zac1 acted synergistically with AP-1, human papillomavirus E2, and hypoxia inducible factor 1 alpha (HIF1α). expression under various conditions, including hypoxia or treatment with phorbol 12-myristate 13-acetate or copper sulfate. Recombinant IL-11-induced phosphorylation of signal transducer and activator of transcription 3 at tyrosine 705 was reduced in a dose-dependent manner in HeLa cells. Cross-talk between Zac1, IL-11, p53, and suppressor of cytokine signaling 3 was differentially affected by copper sulfate, digoxin, and caffeine. Finally, aggressive vs. conventional treatment of OA patients was primarily determined by IL-6 levels. However, we suggest that OA patients with higher IL-11 levels may respond well to conventional treatments, even in the presence of high IL-6.
白细胞介素（IL）-11是细胞因子IL-6家族的成员之一，在正常及多种疾病状态下发挥多效性作用。我们评估了骨关节炎（OA）中的表达调控及IL-11/IL-6比值，以更好地指导临床治疗决策。我们的研究结果表明，Zac1是一种调节细胞凋亡和细胞周期停滞的锌指蛋白，是调控表达的转录因子。Zac1的过表达或敲低分别在HeLa细胞中诱导或抑制表达。Zac1与AP-1、人乳头瘤病毒E2及缺氧诱导因子1α（HIF1α）协同发挥作用。在包括缺氧、用佛波醇12-肉豆蔻酸酯13-乙酸酯或硫酸铜处理等多种条件下的表达。重组IL-11诱导的信号转导及转录激活因子3在酪氨酸705位点的磷酸化在HeLa细胞中呈剂量依赖性降低。Zac1、IL-11、p53及细胞因子信号转导抑制因子3之间的相互作用受到硫酸铜、地高辛和咖啡因的不同影响。最后，OA患者的积极治疗与传统治疗主要由IL-6水平决定。然而，我们认为IL-11水平较高的OA患者可能对传统治疗反应良好，即使存在高IL-6水平。
