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Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli.

Publication ,  Journal Article
Qiu, L-Q; Lai, WS; Bradbury, A; Zeldin, DC; Blackshear, PJ
Published in: J Leukoc Biol
April 2015

TTP is an anti-inflammatory protein that acts by binding to AREs in its target mRNAs, such as Tnf mRNA, and promoting their deadenylation and decay. TNF released from inflammatory cells can then stimulate gene expression in tissue cells, such as fibroblasts. To determine whether TTP could affect the decay of TNF-induced transcripts in fibroblasts, we exposed primary embryonic fibroblasts and stable fibroblast cell lines, derived from WT and TTP KO mice, to TNF. The decay rates of transcripts encoded by several early-response genes, including Cxcl1, Cxcl2, Ier3, Ptgs2, and Lif, were significantly slowed in TTP-deficient fibroblasts after TNF stimulation. These changes were associated with TTP-dependent increases in CXCL1, CXCL2, and IER3 protein levels. The TTP-susceptible transcripts contained multiple, conserved, closely spaced, potential TTP binding sites in their 3'-UTRs. WT TTP, but not a nonbinding TTP zinc finger mutant, bound to RNA probes that were based on the mRNA sequences of Cxcl1, Cxcl2, Ptgs2, and Lif. TTP-promoted decay of transcripts encoding chemokines and other proinflammatory mediators is thus a critical post-transcriptional regulatory mechanism in the response of secondary cells, such as fibroblasts, to TNF released from primary immune cells.

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Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

April 2015

Volume

97

Issue

4

Start / End Page

723 / 736

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tristetraprolin
  • Transcription, Genetic
  • Toll-Like Receptors
  • Recombinant Fusion Proteins
  • RNA, Messenger
  • RNA Stability
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

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Qiu, L.-Q., Lai, W. S., Bradbury, A., Zeldin, D. C., & Blackshear, P. J. (2015). Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli. J Leukoc Biol, 97(4), 723–736. https://doi.org/10.1189/jlb.3A0214-106R
Qiu, Lian-Qun, Wi S. Lai, Alyce Bradbury, Darryl C. Zeldin, and Perry J. Blackshear. “Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli.J Leukoc Biol 97, no. 4 (April 2015): 723–36. https://doi.org/10.1189/jlb.3A0214-106R.
Qiu L-Q, Lai WS, Bradbury A, Zeldin DC, Blackshear PJ. Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli. J Leukoc Biol. 2015 Apr;97(4):723–36.
Qiu, Lian-Qun, et al. “Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli.J Leukoc Biol, vol. 97, no. 4, Apr. 2015, pp. 723–36. Pubmed, doi:10.1189/jlb.3A0214-106R.
Qiu L-Q, Lai WS, Bradbury A, Zeldin DC, Blackshear PJ. Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli. J Leukoc Biol. 2015 Apr;97(4):723–736.

Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

April 2015

Volume

97

Issue

4

Start / End Page

723 / 736

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tristetraprolin
  • Transcription, Genetic
  • Toll-Like Receptors
  • Recombinant Fusion Proteins
  • RNA, Messenger
  • RNA Stability
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice