genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Liver Gene Expression Pattern in a Mouse Psychological Stress Model
Fig. R.1.7: Hepatic repression of antigen
presentation related genes after chronic
stress.
Canonical “Antigen Presentation Pathway” of
Ingenuity Pathway Analysis (adapted from
IPA, Ingenuity Systems, www.ingenuity.com)
displaying genes specifically repressed during
chronic but not during acute stress.
Repression of gene expression is indicated in
green. The following genes are affected: H2-
Aa and H2-Ea (MHC-IIα); Cd74 (CLIP); Psmb9
(LMP2). The blue circle indicates gene
repression for H2-Ab1 (MHC-IIβ), which did
not pass the regulation criteria because of
low expression level.
Increased leukocyte trafficking into the liver of chronically stressed mice
Immediately after acute stress, several markers of leukocyte migration were differentially
regulated in hepatic tissue compared with non-stressed controls. This set included lymphocyte
chemoattractive molecules such as Cxcl11 and Cxl12, which were repressed, or neutrophils
attractive Cxcl1, which was highly expressed after acute but also after chronic stress exposure. An
induction of Vcam1 after acute and chronic stress and of Arhgap5 selectively after repeated
stress as well as the repression of Bcar3 in the liver after acute stress exposure indicated that the
extravasation of leukocytes was facilitated. Additionally, mRNA profiling uncovered a repression
of genes whose products are involved in maintaining the endothelial barrier function such as
claudin 1 (Cldn1), selectively after acute stress, or claudin 2 and 3 after both acute and chronic
stress. To investigate whether these changes in gene expression also caused physiological
changes in leukocyte composition of the liver, immunofluorescence staining was performed
which revealed that no changes of immune cell numbers in the liver were detectable
immediately after a single acute stress session by staining leukocytes with anti-CD45 antibodies
(data not shown). However, in the periportal areas of chronically stressed animals there were
increased numbers of CD45-positive cells, which supports the data of the gene expression
profiling that indicated stress-induced leukocyte migration (data not shown).
Increased oxidative stress in the liver after acute psychological stress exposure is counterregulated
after repeated stress
Inflammatory responses are associated with increased generation of reactive oxygen and
nitrogen species. Gene expression profiling gave hints for increased oxidative stress in the liver of
acutely and chronically stressed mice. Alas1 or As3mt, which are important for the regulation of
the oxidative state, were differentially regulated after acute and chronic stress. The redox
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