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Title: H. pylori infection blocks DNA damage induced apoptosis by T4SS-dependent upregulation of miR-155      
dateReleased:
04-02-2012
description:
The innate immune response against Helicobacter pylori is mainly controlled by pattern recognition receptors that lead to the up-regulation of pro-inflammatory cytokines. A new player in this field is the miR-155 being regulated by TLR ligands in monocytic derived cells influencing certain intracellular pathways by down-regulating targets involved in signaling and development. By using primary bone marrow derived macrophages (BMMs) from mice deficient in the key TLR signals the regulation of miR-155 was explored. Further on the biological impact of a lack of miR-155 in BMMs was analyzed by micro-array studies and apoptosis assays. We observed that miR-155 is up-regulated in response to H. pylori via TLR2 and TLR4 in a NF-κB dependent manner, but also identified a TLR2/TLR4 independent mechanism that was strongly connected to a functional TypeIV secretion system. Down-stream the high expression of miR-155 down-regulated many mRNA targets during H. pylori infection. Thereby we could validate Tspan14, Lpin1, and Pmaip1 as new targets of miR-155 and identified their binding site. These and other already published targets showed a substantial pro-apoptotic potential. We observed that H. pylori infected wild type BMMs were much more resistant to DNA damage induced apoptosis by cisplatin when compared to their respective miR-155-/- BMMs. Our data strongly suggests that there is an additional innate immune mechanism of BMMs leading to the upregulation of the anti-apoptotic miR-155 that causes resistance to DNA damage in BMMs. Microarray experiments were performed as dual-color hybridizations. To compensate for dye-specific effects, an independent dye-reversal color-swap was applied. Bone marrow derived macrophages were 'in vitro' infected with H.pylori P12 and the expression changes were measured.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-29388
refinement:
raw
alternateIdentifiers:
29388
keywords:
functional genomics
dateModified:
05-03-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-MEXP-724
name:
Agilent Whole Mouse Genome Microarray 4x44K 014868 G4122F (annotation from 02.2007)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-29388/E-GEOD-29388.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-29388/E-GEOD-29388.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29388
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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