title: Functional regulation of Zfp36l1 and Zfp36l2 in response to lipopolysaccharide in mouse RAW264.7 macrophages.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  Ttp 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Pediatric Immunology and Nephrology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Road, Beitou District, Taipei, 112 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, Taipei, 112 Taiwan.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan.
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan.
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Su
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chiang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, No.128, Sec.2, Academia Road, Nankang, Taipei, 11529 Taiwan.
authors.forename: Nien-Yi
authors.initials: NY
authors.lastname: Lin
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, No.128, Sec.2, Academia Road, Nankang, Taipei, 11529 Taiwan.
authors.forename: Shun-Chang
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan.
authors.forename: Geen-Dong
authors.initials: GD
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No.1 Sec. 4 Roosevelt Road, Taipei, 10617 Taiwan ; Institute of Biological Chemistry, Academia Sinica, No.128, Sec.2, Academia Road, Nankang, Taipei, 11529 Taiwan.
authors.forename: Ching-Jin
authors.initials: CJ
authors.lastname: Chang
keywords: Macrophage; Mkp-1; Tristetraprolin; Zfp36l1; Zfp36l2; p38 MAPK