Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Май 5, 2020
Gasdermin-D
(GSDMD)
in
inflammasome-activated
macrophages
is
cleaved
by
caspase-1
to
generate
N-GSDMD
fragments.
then
oligomerizes
the
plasma
membrane
(PM)
form
pores
that
increase
permeability,
leading
pyroptosis
and
IL-1β
release.
In
contrast,
we
report
although
required
for
secretion
NLRP3-activated
human
murine
neutrophils,
does
not
localize
PM
or
permeability
pyroptosis.
Instead,
biochemical
microscopy
studies
reveal
neutrophils
predominantly
associates
with
azurophilic
granules
LC3+
autophagosomes.
trafficking
causes
leakage
of
neutrophil
elastase
into
cytosol,
resulting
secondary
cleavage
GSDMD
an
alternatively
product.
Genetic
analyses
using
ATG7-deficient
cells
indicate
secrete
via
autophagy-dependent
mechanism.
These
findings
fundamental
differences
between
underlie
neutrophil-specific
functions
during
inflammasome
activation.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Июль 12, 2021
Abstract
Cancer
development
and
its
response
to
therapy
are
regulated
by
inflammation,
which
either
promotes
or
suppresses
tumor
progression,
potentially
displaying
opposing
effects
on
therapeutic
outcomes.
Chronic
inflammation
facilitates
progression
treatment
resistance,
whereas
induction
of
acute
inflammatory
reactions
often
stimulates
the
maturation
dendritic
cells
(DCs)
antigen
presentation,
leading
anti-tumor
immune
responses.
In
addition,
multiple
signaling
pathways,
such
as
nuclear
factor
kappa
B
(NF-kB),
Janus
kinase/signal
transducers
activators
transcription
(JAK-STAT),
toll-like
receptor
(TLR)
cGAS/STING,
mitogen-activated
protein
kinase
(MAPK);
factors,
including
cytokines
(e.g.,
interleukin
(IL),
interferon
(IFN),
necrosis
(TNF)-α),
chemokines
C-C
motif
chemokine
ligands
(CCLs)
C-X-C
(CXCLs)),
growth
factors
vascular
endothelial
(VEGF),
transforming
(TGF)-β),
inflammasome;
well
metabolites
prostaglandins,
leukotrienes,
thromboxane,
specialized
proresolving
mediators
(SPM),
have
been
identified
pivotal
regulators
initiation
resolution
inflammation.
Nowadays,
local
irradiation,
recombinant
cytokines,
neutralizing
antibodies,
small-molecule
inhibitors,
DC
vaccines,
oncolytic
viruses,
TLR
agonists,
SPM
developed
specifically
modulate
in
cancer
therapy,
with
some
these
already
undergoing
clinical
trials.
Herein,
we
discuss
crosstalk
between
processes.
We
also
highlight
potential
targets
for
harnessing
cancer.
European Journal of Immunology,
Год журнала:
2019,
Номер
49(10), С. 1457 - 1973
Опубликована: Окт. 1, 2019
These
guidelines
are
a
consensus
work
of
considerable
number
members
the
immunology
and
flow
cytometry
community.
They
provide
theory
key
practical
aspects
enabling
immunologists
to
avoid
common
errors
that
often
undermine
immunological
data.
Notably,
there
comprehensive
sections
all
major
immune
cell
types
with
helpful
Tables
detailing
phenotypes
in
murine
human
cells.
The
latest
techniques
applications
also
described,
featuring
examples
data
can
be
generated
and,
importantly,
how
analysed.
Furthermore,
tips,
tricks
pitfalls
avoid,
written
peer-reviewed
by
leading
experts
field,
making
this
an
essential
research
companion.
Cell Death and Disease,
Год журнала:
2019,
Номер
10(9)
Опубликована: Сен. 9, 2019
Abstract
Programmed
cell
death
(PCD)
refers
to
the
way
in
which
cells
die
depending
on
specific
genes
encoding
signals
or
activities.
Apoptosis,
autophagy,
and
pyroptosis
are
all
mechanisms
of
PCD.
Among
these
mechanisms,
is
mediated
by
gasdermin
family,
accompanied
inflammatory
immune
responses.
The
relationship
between
cancer
complex,
effects
vary
different
tissues
genetic
backgrounds.
On
one
hand,
can
inhibit
occurrence
development
tumors;
other
as
a
type
proinflammatory
death,
form
suitable
microenvironment
for
tumor
growth
thus
promote
growth.
In
addition,
induction
also
considered
potential
treatment
strategy.
Studies
have
shown
that
DFNA5
(nonsyndromic
hearing
impairment
protein
5)/GSDME
(Gasdermin-E)
mRNA
methylation
results
lower
expression
levels
DFNA5/GSDME
most
than
normal
cells,
making
it
difficult
activate
cells.
During
malignant
tumors,
appropriate
chemotherapeutic
drugs
be
selected
according
DFNA5/GSDME,
upregulated
thereby
increasing
sensitivity
reducing
drug
resistance.
Therefore,
induced
may
play
predominant
role
cancer.
Here,
we
review
latest
research
anti-
protumor
its
applications
treatment.
Circulation Research,
Год журнала:
2018,
Номер
122(12), С. 1722 - 1740
Опубликована: Июнь 7, 2018
Inflammation
is
an
important
driver
of
atherosclerosis,
the
underlying
pathology
cardiovascular
diseases.
Therefore,
therapeutic
targeting
inflammatory
pathways
suggested
to
improve
outcomes
in
patients
with
This
concept
was
recently
proven
by
CANTOS
(Canakinumab
Anti-Inflammatory
Thrombosis
Outcomes
Study),
which
demonstrated
potential
monoclonal
IL
(interleukin)-1β-neutralizing
antibody
canakinumab.
IL-1β
and
other
IL-1
family
cytokines
are
vascular
systemic
mediators,
contribute
atherogenesis.
The
NLRP3
(NOD
[nucleotide
oligomerization
domain]-,
LRR
[leucine-rich
repeat]-,
PYD
[pyrin
domain]-containing
protein
3)
inflammasome,
innate
immune
signaling
complex,
key
mediator
cytokine
production
atherosclerosis.
activated
various
endogenous
danger
signals
abundantly
present
atherosclerotic
lesions,
such
as
oxidized
low-density
lipoprotein
cholesterol
crystals.
Consequently,
inflammasome
activation
contributes
response
driving
atherosclerosis
development
progression.
Here,
we
review
mechanisms
proinflammatory
context
discuss
treatment
possibilities
light
positive
trial.
Annual Review of Immunology,
Год журнала:
2020,
Номер
38(1), С. 567 - 595
Опубликована: Фев. 4, 2020
Caspases
are
a
family
of
conserved
cysteine
proteases
that
play
key
roles
in
programmed
cell
death
and
inflammation.
In
multicellular
organisms,
caspases
activated
via
macromolecular
signaling
complexes
bring
inactive
procaspases
together
promote
their
proximity-induced
autoactivation
proteolytic
processing.
Activation
ultimately
results
execution
death,
the
nature
this
is
determined
by
specific
involved.
Pioneering
new
research
has
unraveled
distinct
cross
talk
regulation
inflammation,
innate
immune
responses.
In-depth
understanding
these
mechanisms
essential
to
foster
development
precise
therapeutic
targets
treat
autoinflammatory
disorders,
infectious
diseases,
cancer.
This
review
focuses
on
governing
caspase
activation
with
special
emphasis
recent
progress
caspase-driven
gasdermin
D-induced
pyroptosis.
Frontiers in Immunology,
Год журнала:
2018,
Номер
9
Опубликована: Окт. 16, 2018
Pattern
Recognition
Receptors
(PRRs)
are
proteins
capable
of
recognizing
molecules
frequently
found
in
pathogens
(the
so-called
Pathogen-Associated
Molecular
Patterns
-
PAMPs),
or
released
by
damaged
cells
Damage-Associated
DAMPs).
They
emerged
phylogenetically
prior
to
the
appearance
adaptive
immunity
and,
therefore,
considered
part
innate
immune
system.
Signals
derived
from
engagement
PRRs
on
activate
microbicidal
and
pro-inflammatory
responses
required
eliminate
or,
at
least,
contain
infectious
agents.
Molecularly
controlled
forms
cell
death
also
a
very
ancestral
mechanism
involved
key
aspects
physiology
multicellular
organism,
including
elimination
unwanted,
infected
cells.
Interestingly,
each
form
has
its
particular
effect
inflammation
development
responses.
In
this
mini-review
article,
we
discuss
some
molecular
interplay
between
machinery
signals
initiated
activation
PAMPs
DAMPs.
