PMID- 19945750
OWN - NLM
STAT- MEDLINE
DCOM- 20100223
LR  - 20171116
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 47
IP  - 5
DP  - 2010 Feb
TI  - The RNA binding protein tristetraprolin influences the activation state of murine 
      dendritic cells.
PG  - 1161-70
LID - 10.1016/j.molimm.2009.11.002 [doi]
AB  - Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state 
      conditions. Upon triggering by activation signals they initiate strong immune 
      responses. The activation of DCs is accompanied by a rapid upregulation of 
      proinflammatory cytokines, which were shown in other cell types to be regulated 
      by mechanisms at the transcriptional and posttranscriptional level. 
      Tristetraprolin (TTP), an important RNA binding protein, is involved in the 
      regulation of mRNA stability of such cytokines. In this study we analyzed the 
      significance of TTP for mouse DCs, which were derived from TTP(-/-) and WT bone 
      marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP(-/-) mice expressed 
      lower levels of mRNAs encoding the costimulatory molecules CD40 and CD86 and 
      surprisingly also the canonical TTP targets TNF-alpha and IL-10 as compared with 
      WT DCs. On the protein level, both DC populations expressed comparable amounts of 
      CD80 and CD86 and of either cytokine, but TTP(-/-) DCs expressed less MHCII than 
      WT DCs. On the other hand, TTP(-/-) DCs displayed elevated expression of other 
      TTP target mRNAs like IL-1beta, c-fos and Mkp-1. Stimulation of BM-DCs of either 
      genotype with lipopolysaccharide resulted in a rapid upregulation to a comparable 
      extent of all molecules monitored so far, except for c-fos mRNA. Subsequent mRNA 
      decay analysis revealed gene-specific differences in mRNA stability, which was 
      influenced by the presence of TTP and the activation state of the DCs. 
      Unstimulated TTP(-/-) DCs exerted a markedly lower allogeneic T cell stimulatory 
      potential than WT DCs. Moreover, TTP(-/-) DCs induced an altered cytokine pattern 
      in cocultures of DCs and T cells. However, allogeneic T cells primed by 
      unstimulated DCs of either genotype were equally refractory to restimulation and 
      suppressed the proliferation of naive T cells to the same extent. Thus, the 
      findings of this study lend support to the interpretation that without external 
      stimulation antigen presenting activity in DCs in the presence of TTP is more 
      pronounced than in its absence and that posttranscriptional regulation 
      contributes to the control of gene expression in DCs.
CI  - (c) 2009 Elsevier Ltd. All rights reserved.
FAU - Bros, Matthias
AU  - Bros M
AD  - Department of Dermatology, University Medical Center of the Johannes 
      Gutenberg-University, Mainz, Germany. mbros@uni-mainz.de
FAU - Wiechmann, Nadine
AU  - Wiechmann N
FAU - Besche, Verena
AU  - Besche V
FAU - Art, Julia
AU  - Art J
FAU - Pautz, Andrea
AU  - Pautz A
FAU - Grabbe, Stephan
AU  - Grabbe S
FAU - Kleinert, Hartmut
AU  - Kleinert H
FAU - Reske-Kunz, Angelika B
AU  - Reske-Kunz AB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091128
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Tristetraprolin)
RN  - 0 (Zfp36 protein, mouse)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dusp1 protein, mouse)
SB  - IM
MH  - Animals
MH  - B7-2 Antigen/biosynthesis/immunology
MH  - CD40 Antigens/biosynthesis/immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Dual Specificity Phosphatase 1/biosynthesis/immunology
MH  - Female
MH  - Histocompatibility Antigens Class II/biosynthesis/immunology
MH  - Interleukin-1beta/biosynthesis/immunology
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-fos/biosynthesis/immunology
MH  - RNA Stability/drug effects/genetics/*immunology
MH  - RNA, Messenger/biosynthesis/*immunology
MH  - RNA-Binding Proteins/genetics/*immunology/metabolism
MH  - Tristetraprolin/genetics/*immunology/metabolism
MH  - Up-Regulation/drug effects/immunology
EDAT- 2009/12/01 06:00
MHDA- 2010/02/24 06:00
CRDT- 2009/12/01 06:00
PHST- 2009/05/01 00:00 [received]
PHST- 2009/09/15 00:00 [revised]
PHST- 2009/11/03 00:00 [accepted]
PHST- 2009/12/01 06:00 [entrez]
PHST- 2009/12/01 06:00 [pubmed]
PHST- 2010/02/24 06:00 [medline]
AID - S0161-5890(09)00811-6 [pii]
AID - 10.1016/j.molimm.2009.11.002 [doi]
PST - ppublish
SO  - Mol Immunol. 2010 Feb;47(5):1161-70. doi: 10.1016/j.molimm.2009.11.002. Epub 2009 
      Nov 28.