PMID- 20209161
OWN - NLM
STAT- MEDLINE
DCOM- 20110111
LR  - 20220310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 3
DP  - 2010 Mar 2
TI  - Helicobacter pylori induces miR-155 in T cells in a cAMP-Foxp3-dependent manner.
PG  - e9500
LID - 10.1371/journal.pone.0009500 [doi]
LID - e9500
AB  - Amongst the most severe clinical outcomes of life-long infections with 
      Helicobacter pylori is the development of peptic ulcers and gastric 
      adenocarcinoma--diseases often associated with an increase of regulatory T cells. 
      Understanding H. pylori-driven regulation of T cells is therefore of crucial 
      clinical importance. Several studies have defined mammalian microRNAs as key 
      regulators of the immune system and of carcinogenic processes. Hence, we aimed 
      here to identify H. pylori-regulated miRNAs, mainly in human T cells. MicroRNA 
      profiling of non-infected and infected human T cells revealed H. pylori infection 
      triggers miR-155 expression in vitro and in vivo. By using single and double H. 
      pylori mutants and the corresponding purified enzymes, the bacterial vacuolating 
      toxin A (VacA) and gamma-glutamyl transpeptidase (GGT) plus lipopolysaccharide 
      (LPS) tested positive for their ability to regulate miR-155 and Foxp3 expression 
      in human lymphocytes; the latter being considered as the master regulator and 
      marker of regulatory T cells. RNAi-mediated knockdown (KD) of the Foxp3 
      transcription factor in T cells abolished miR-155 expression. Using adenylate 
      cyclase inhibitors, the miR-155 induction cascade was shown to be dependent on 
      the second messenger cyclic adenosine monophosphate (cAMP). Furthermore, we found 
      that miR-155 directly targets the protein kinase A inhibitor alpha (PKIalpha) 
      mRNA in its 3'UTR, indicative of a positive feedback mechanism on the cAMP 
      pathway. Taken together, our study describes, in the context of an H. pylori 
      infection, a direct link between Foxp3 and miR-155 in human T cells and 
      highlights the significance of cAMP in this miR-155 induction cascade.
FAU - Fassi Fehri, Lina
AU  - Fassi Fehri L
AD  - Department of Molecular Biology, Max Planck Institute for Infection Biology, 
      Berlin, Germany.
FAU - Koch, Manuel
AU  - Koch M
FAU - Belogolova, Elena
AU  - Belogolova E
FAU - Khalil, Hany
AU  - Khalil H
FAU - Bolz, Christian
AU  - Bolz C
FAU - Kalali, Behnam
AU  - Kalali B
FAU - Mollenkopf, Hans J
AU  - Mollenkopf HJ
FAU - Beigier-Bompadre, Macarena
AU  - Beigier-Bompadre M
FAU - Karlas, Alexander
AU  - Karlas A
FAU - Schneider, Thomas
AU  - Schneider T
FAU - Churin, Yuri
AU  - Churin Y
FAU - Gerhard, Markus
AU  - Gerhard M
FAU - Meyer, Thomas F
AU  - Meyer TF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100302
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3' Untranslated Regions)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MIRN155 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn155 microRNA, mouse)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Cyclic AMP/*metabolism
MH  - Forkhead Transcription Factors/*metabolism
MH  - *Gene Expression Regulation, Bacterial
MH  - Helicobacter pylori/*metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Lipopolysaccharides/chemistry
MH  - Mice
MH  - MicroRNAs/*biosynthesis/genetics
MH  - Models, Biological
MH  - Mutation
MH  - T-Lymphocytes/*metabolism/*microbiology
PMC - PMC2830477
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/03/09 06:00
MHDA- 2011/01/12 06:00
PMCR- 2010/03/02
CRDT- 2010/03/09 06:00
PHST- 2009/11/20 00:00 [received]
PHST- 2010/02/10 00:00 [accepted]
PHST- 2010/03/09 06:00 [entrez]
PHST- 2010/03/09 06:00 [pubmed]
PHST- 2011/01/12 06:00 [medline]
PHST- 2010/03/02 00:00 [pmc-release]
AID - 09-PONE-RA-14404R1 [pii]
AID - 10.1371/journal.pone.0009500 [doi]
PST - epublish
SO  - PLoS One. 2010 Mar 2;5(3):e9500. doi: 10.1371/journal.pone.0009500.