Zac1 regulates IL-11 expression in osteoarthritis
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Chun-Lin Kuo1,2, Shu-Ting Liu3, Yung-Lung Chang3, Chia-Chun Wu2 and Shih-Ming Huang1,3
1Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, Republic of China
2Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China
3Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of China
Shih-Ming Huang, email: [email protected]
Keywords: zac1; IL-11; HeLa; osteoarthritis; IL-6
Received: March 30, 2018 Accepted: July 29, 2018 Published: August 21, 2018
Interleukin (IL)-11, a member of the IL-6 family of cytokines, exerts pleiotropic effects under normal and various disease conditions. We assessed IL-11 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 IL-11 expression. Zac1 overexpression or knockdown respectively induced or suppressed IL-11 expression in HeLa cells. Zac1 acted synergistically with AP-1, human papillomavirus E2, and hypoxia inducible factor 1 alpha (HIF1α). IL-11 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.
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