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| Identifier |
000380976 |
| Title |
Ο ρόλος του TNFa στην απόπτωση των ψωριακών κερατινοκυττάρων |
| Alternative Title |
The role of TNFA in the apoptosis of the psoriatic keratinocytes |
|
Author
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Κοκολάκης, Γεώργιος
|
|
Thesis advisor
|
Κρύγκερ Σαμπινέ-Κρασαγάκη
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|
Reviewer
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Χαλεπάκης, Γεώργιος
Τσατσάνης, Χρήστος
Θερμού, Κυριακή
Σταθόπουλος, Ευστάθιος
Κρασαγάκης, Κων/νος
Χατζή, Λήδα
|
| Abstract |
Psoriasis
is
a
common
immune-‐mediated
skin
disease
affecting
about
3-‐5%
of
the
western
population.
The
prominent
role
of
the
TNFα
as
a
key
mediator
of
the
disease
has
been
proven
by
the
efficacy
of
the
therapies
that
inhibit
its
activity.
Prompted
by
previous
results
of
our
group
we
intended
to
further
identify
the
effects
of
TNF-‐blockade
in
the
apoptosis
of
the
psoriatic
keratinocytes.
Serial
biopsies
from
psoriasis
patients
before
and
during
the
treatment
with
infliximab
were
obtained
and
immunohistolically
stained
for
the
apoptotic
proteins
P53,
AIF,
Bax,
NFκB,
Bcl-‐2
and
BCLXL.
A
computerized
system
of
pixelwise
image
analysis
of
the
stainings
was
established.
The
epidermal
thickness
was
digitally
estimated
and
correlated
with
the
clinical
index
PASI.
Furthermore,
primary
isolated
normal
human
keratinocytes
were
cultured
with
or
without
TNFα
and
then
treated
with
infliximab.
Cell
proliferation
assay,
Apoptosis-‐ELISA,
cytotoxicity
assay
and
western-‐blot
for
the
quantification
of
apoptotic
proteins
were
performed.
The
digital
analysis
system
provided
parametrical
values
of
the
stainings,
allowing
in
this
way,
the
in-‐depth
characterisation
of
the
differences
in
the
expression
of
the
proteins
within
the
different
epidermal
compartments
throughout
the
treatment.
A
statistically
significant
upregulation
of
the
proapoptotic
proteins
simultaneously
with
a
downregulation
of
the
antiapoptotic
proteins
have
been
observed.
Before
treatment
a
remarked
difference
compared
with
the
non-‐lesional
skin
could
be
shown.
However,
after
treatment
lesional
skin
simulates
the
non-‐lesional
skin.
The
expression
of
the
apoptotic
proteins
differed
significantly
between
the
distinct
epidermal
compartments.
PASI
score
was
significantly
correlated
to
the
epidermal
thickness
at
the
predetermined
time-‐points.
In
the
level
of
the
keratinocyte
cultures
decreased
proliferation
and
increased
apoptotic
rates
could
be
observed
after
the
treatment
with
infliximab
in
TNFα
pre-‐treated
cells.
The
effect
seemed
to
be
driven
by
the
NFκB
proceeding.
However,
the
in
vitro
model
failed
to
simulate
the
in
vivo
conditions.
In
the
present
project,
it
could
be
shown
that
anti-‐TNF
treatments
–
besides
their
immunemodulating
effects
–
they
influenced
the
impaired
apoptotic
balance
of
the
psoriatic
keratinocytes.
Proapoptotic
proteins
(P53,
AIF,
Bax)
were
upregulated,
whereas
the
antiapoptotic
ones
(NFκB,
Bcl-‐2,
BclXL)
were
suppressed,
inciting
the
keratinocytes
to
overcome
the
resistance
to
apoptotic
stimuli.
These
events
occurred
in
line
with
the
restoration
of
the
epidermal
architecture
and
the
decrease
of
the
epidermal
thickness
correlated
with
the
improvement
of
the
PASI
score.
The
in
vitro
experiments
verified
the
apoptotic
effect
of
TNF-‐blockade.
|
| Language |
Greek |
| Subject |
Apoptosis |
|
Dermatology |
|
Infliximab |
|
Keratinocytes |
|
Pathogenesis |
|
Psoriasis |
|
TNFa |
|
Therapy |
|
Απόπτωση |
|
Ινφλιξιμάμπη |
|
Κερατινοκύτταρα |
|
Παθογένεση |
|
Ψωρίαση |
| Issue date |
2013-07-16 |
| Collection
|
School/Department--School of Medicine--Department of Medicine--Doctoral theses
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|
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Type of Work--Doctoral theses
|
| Permanent Link |
https://elocus.lib.uoc.gr//dlib/0/e/a/metadata-dlib-1383548467-444885-3901.tkl
|
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