Functional regulation of Zfp36l1 and Zfp36l2 in response to lipopolysaccharide in mouse RAW264.7 macrophages

Journal of Inflammation

Research

Hsin-Hui Wang¹  Yu-Lun Su²  Yan-Yun Wu²  Pei-Yu Chiang²  Geen-Dong Chang²  Kuan-Ting Wang²  Ching-Jin Chang³  Nien-Yi Lin⁴  Shun-Chang Wang⁴ 

[1] Department of Pediatrics, Division of Pediatric Immunology and Nephrology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road, Beitou District, 112, Taipei, Taiwan;Department of Pediatrics, Faculty of Medicine, School of Medicine, and Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, No.155, Sec.2, Linong Street, Beitou District, 112, Taipei, Taiwan;Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, 10617, Taipei, Taiwan;Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, 10617, Taipei, Taiwan;Institute of Biological Chemistry, Academia Sinica, No.128, Sec.2, Academia Road, Nankang, 11529, Taipei, Taiwan;Institute of Biological Chemistry, Academia Sinica, No.128, Sec.2, Academia Road, Nankang, 11529, Taipei, Taiwan;

关键词: Tristetraprolin;    Zfp36l1;    Zfp36l2;    Mkp-1;    p38 MAPK;    Macrophage;   

DOI  :  10.1186/s12950-015-0088-x

 received in 2015-04-21, accepted in 2015-06-25,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe tristetraprolin (TTP) family of mRNA-binding proteins contains three major members, Ttp, Zfp36l1, and Zfp36l2. Ttp down-regulates the stability of AU-rich element–containing mRNAs and functions as an anti-inflammation regulator.MethodsTo examine whether other TTP family proteins also play roles in the inflammatory response, their expression profiles and the possible mRNA targets were determined in the knockdown cells.ResultsTtp mRNA and protein were highly induced by lipopolysaccharide (LPS), whereas Zfp36l1 and Zfp36l2 mRNAs were down-regulated and their proteins were phosphorylated during early lipopolysaccharide stimulation. Biochemical and functional analyses exhibited that the decrease of Zfp36l2 mRNA was cross-regulated by Ttp. Knockdown of Zfp36l1 and Zfp36l2 increased the basal level of Mkp-1 mRNAs by prolonging its half-life. Increasing the expression of Mkp-1 inhibited the activation of p38 MAPK under lipopolysaccharide stimulation and down-regulated Tnfα, and Ttp mRNA. In addition, hyper-phosphorylation of Zfp36l1 might stabilize Mkp-1 expression by forming a complex with the adapter protein 14-3-3 and decreasing the interaction with deadenylase Caf1a.ConclusionsOur findings imply that the expression and phosphorylation of Zfp36l1 and Zfp36l2 may modulate the basal level of Mkp-1 mRNA to control p38 MAPK activity during lipopolysaccharide stimulation, which would affect the inflammatory mediators production. Zfp36l1 and Zfp36l2 are important regulators of the innate immune response.

【 授权许可】

Unknown   
© Wang et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.