Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: March 21, 2025
There
has
been
abundant
research
on
the
variety
of
programmed
cell
death
pathways.
Apoptosis,
pyroptosis,
and
necroptosis
under
action
caspase
family
are
essential
for
innate
immune
response.
Caspases
classified
into
inflammatory
caspase-1/4/5/11,
apoptotic
caspase-3/6/7,
caspase-2/8/9/10.
Although
is
not
caspase-dependent
to
transmit
signals,
it
can
cross-link
with
pyroptosis
apoptosis
signals
regulation
caspase-8.
An
increasing
number
studies
have
reiterated
involvement
in
acute
lung
injuries
caused
by
bacterial
viral
infections,
blood
transfusion,
ventilation,
which
influenced
noxious
stimuli
that
activate
or
inhibit
engagement
pathways,
leading
subsequent
injury.
This
article
reviews
role
caspases
implicated
diverse
mechanisms
injury
status
relevant
inhibitors
against
target
proteins
described
mechanisms.
The
findings
this
review
may
help
delineating
novel
therapeutic
targets
Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: Oct. 30, 2019
Sepsis
is
a
deadly
inflammatory
syndrome
caused
by
an
exaggerated
immune
response
to
infection.
Much
has
been
focused
on
host
pathogens
mediated
through
the
interaction
of
pathogen-associated
molecular
patterns
(PAMPs)
and
pattern
recognition
receptors
(PRRs).
PRRs
are
also
activated
nuclear,
mitochondrial,
cytosolic
proteins,
known
as
damage-associated
(DAMPs)
that
released
from
cells
during
sepsis.
Some
well
described
members
DAMP
family
extracellular
cold-inducible
RNA-binding
protein
(eCIRP),
high
mobility
group
box
1
(HMGB1),
histones,
adenosine
triphosphate
(ATP).
DAMPs
cell
inflammasome
activation
or
passively
following
death.
Similarly,
neutrophil
traps
(NETs)
neutrophils
inflammation.
NETs
webs
DNA
decorated
with
myeloperoxidase,
elastase.
Although
contribute
pathogen
clearance,
excessive
NET
formation
promotes
inflammation
tissue
damage
in
Here,
we
review
their
crosstalk
sepsis
respect
sources,
activation,
release,
function.
A
clear
understating
DAMPs,
crucial
for
understanding
pathophysiology
development
novel
therapeutics.
APOPTOSIS,
Journal Year:
2021,
Volume and Issue:
26(3-4), P. 152 - 162
Published: March 13, 2021
Abstract
Damage-associated
molecular
patterns
(DAMPs)
are
endogenous
molecules
which
foment
inflammation
and
associated
with
disorders
in
sepsis
cancer.
Thus,
therapeutically
targeting
DAMPs
has
potential
to
provide
novel
effective
treatments.
When
establishing
anti-DAMP
strategies,
it
is
important
not
only
focus
on
the
as
inflammatory
mediators
but
also
take
into
account
underlying
mechanisms
of
their
release
from
cells
tissues.
can
be
released
passively
by
membrane
rupture
due
necrosis/necroptosis,
although
appear
differ
between
DAMPs.
Other
types
cell
death,
such
apoptosis,
pyroptosis,
ferroptosis
NETosis,
contribute
DAMP
release.
In
addition,
some
exported
actively
live
exocytosis
secretory
lysosomes
or
exosomes,
ectosomes,
activation
channel
pores.
Here
we
review
shared
DAMP-specific
reported
literature
for
high
mobility
group
box
1,
ATP,
extracellular
cold-inducible
RNA-binding
protein,
histones,
heat
shock
proteins,
RNAs
cell-free
DNA.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
22(2), P. 559 - 559
Published: Jan. 8, 2021
Neutrophils
are
primary
effector
cells
of
innate
immunity
and
fight
infection
by
phagocytosis
degranulation.
Activated
neutrophils
also
release
neutrophil
extracellular
traps
(NETs)
in
response
to
a
variety
stimuli.
These
NETs
net-like
complexes
composed
cell-free
DNA,
histones
granule
proteins.
Besides
the
evolutionarily
conserved
mechanism
capture
eliminate
pathogens,
associated
with
pathophysiological
processes
various
diseases.
Here,
we
elucidate
mechanisms
NET
formation
their
different
implications
disease.
We
focused
on
autoinflammatory
cardiovascular
disorders
as
leading
cause
death.
Neutrophil
not
only
present
diseases
but
play
an
essential
role
atherosclerotic
plaque
formation,
arterial
venous
thrombosis,
well
development
progression
abdominal
aortic
aneurysms.
Furthermore,
NETosis
can
be
considered
source
autoantigens
maintains
inflammatory
milieu
promoting
autoimmune
Indeed,
there
is
further
need
for
research
into
balance
between
induction,
inhibition,
degradation
order
pharmacologically
target
compounds
without
impairing
patient's
immune
defense.
This
review
may
interest
both
basic
scientists
clinicians
stimulate
translational
innovative
clinical
approaches.
JCI Insight,
Journal Year:
2020,
Volume and Issue:
5(5)
Published: Feb. 6, 2020
Extracellular
cold-inducible
RNA-binding
protein
(eCIRP)
is
a
recently
discovered
damage-associated
molecular
pattern.
Understanding
the
precise
mechanism
by
which
it
exacerbates
inflammation
essential.
Here
we
identified
that
eCIRP
new
biologically
active
endogenous
ligand
of
triggering
receptor
expressed
on
myeloid
cells-1
(TREM-1),
fueling
in
sepsis.
Surface
plasmon
resonance
revealed
strong
binding
affinity
between
and
TREM-1,
fluorescence
energy
transfer
assay
confirmed
eCIRP's
interaction
with
TREM-1
macrophages.
Targeting
its
siRNA
or
decoy
peptide,
LP17,
using
TREM-1–/–
mice
dramatically
reduced
eCIRP-induced
inflammation.
We
developed
potentially
novel
7-aa
peptide
derived
from
human
eCIRP,
M3,
blocked
eCIRP.
M3
suppressed
induced
agonist
antibody
cross-linking
murine
macrophages
peripheral
blood
monocytes.
also
inhibited
systemic
tissue
injury.
Treatment
further
protected
sepsis,
improved
acute
lung
injury,
increased
survival.
Thus,
have
to
block
eCIRP–TREM-1
improve
outcomes
Cells,
Journal Year:
2021,
Volume and Issue:
10(10), P. 2763 - 2763
Published: Oct. 15, 2021
Pulmonary
epithelial
cells
are
widely
considered
to
be
the
first
line
of
defence
in
lung
and
responsible
for
coordinating
innate
immune
response
injury
subsequent
repair.
Consequently,
communicate
with
multiple
cell
types
including
fibroblasts
promote
acute
inflammation
normal
wound
healing
damage.
However,
aberrant
death
damage
hallmarks
pulmonary
disease,
necrotic
cellular
senescence
contributing
disease
pathogenesis
numerous
respiratory
diseases
such
as
idiopathic
fibrosis
(IPF),
chronic
obstructive
(COPD)
coronavirus
(COVID)-19.
In
this
review,
we
summarise
literature
that
demonstrates
plays
a
pivotal
role
dysregulation
leading
tissue
destruction
abnormal
remodelling
several
diseases.
Specifically,
highlight
epithelial-derived
damage-associated
molecular
patterns
(DAMPs)
shaping
assess
their
contribution
inflammatory
fibrotic
signalling
pathways
lung.
Journal of Molecular Medicine,
Journal Year:
2021,
Volume and Issue:
99(10), P. 1373 - 1384
Published: July 13, 2021
Abstract
Pulmonary
fibrosis
is
a
chronic
debilitating
condition
characterized
by
progressive
deposition
of
connective
tissue,
leading
to
steady
restriction
lung
elasticity,
decline
in
function,
and
median
survival
4.5
years.
The
causes
pulmonary
are
inhalation
foreign
particles
(such
as
silicosis
pneumoconiosis),
infections
post
COVID-19),
autoimmune
diseases
systemic
the
tissue),
idiopathic
fibrosis.
therapeutics
currently
available
for
only
modestly
slow
progression
disease.
This
review
centered
on
interplay
damage-associated
molecular
pattern
(DAMP)
molecules,
Toll-like
receptor
4
(TLR4),
inflammatory
cytokines
TNF-α,
IL-1β,
IL-17)
they
contribute
pathogenesis
fibrosis,
possible
avenues
develop
effective
that
disrupt
this
interplay.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: June 29, 2022
Sepsis
is
characterized
by
life-threatening
organ
dysfunction
caused
a
dysregulated
host
response
to
infection.
Extracellular
cold-inducible
RNA-binding
protein
(eCIRP)
damage-associated
molecular
pattern
(DAMP)
that
promotes
inflammation
and
induces
cell
death
via
apoptosis,
NETosis,
and/or
pyroptosis.
Ferroptosis
form
of
regulated
the
accumulation
lipid
peroxide
on
cellular
membranes.
We
hypothesize
eCIRP
ferroptosis
in
macrophages
lung
tissue
during
sepsis.
RAW
264.7
cells
stimulated
with
recombinant
murine
(rm)
CIRP
significantly
decreased
expression
glutathione
peroxidase
4
(GPX4),
negative
regulator
ferroptosis,
increased
reactive
oxygen
species
(ROS)
TLR4
dependent
manner.
In
TLR4-/-
peritoneal
macrophages,
depression
GPX4
increase
ROS
levels
were
attenuated
after
rmCIRP-treatment
compared
WT
macrophages.
rmCIRP
also
induced
which
was
corrected
inhibitor,
ferrostatin-1
(Fer-1).
Intraperitoneal
injection
tissue,
whereas
reduced
Fer-1
treatment.
decreased,
while
malondialdehyde
(MDA),
iron
levels,
injury
scores
lungs
mice
cecal
ligation
puncture
(CLP)-induced
sepsis
CIRP-/-
mice.
Treatment
C23,
specific
CLP
alleviated
decrease
MDA
tissue.
These
findings
suggest
septic
decreasing
increasing
ROS.
Therefore,
regulation
targeting
may
provide
new
therapeutic
approach
other
inflammatory
diseases.
Cell Death and Disease,
Journal Year:
2022,
Volume and Issue:
13(5)
Published: May 2, 2022
Distinct
types
of
immune
responses
are
activated
by
infections,
which
cause
the
development
type
I,
II,
or
III
inflammation,
regulated
Th1,
Th2,
Th17
helper
T
cells
and
ILC1,
ILC2
ILC3
cells,
respectively.
While
classification
to
different
groups
pathogens
is
widely
accepted,
subtypes
response
elicited
sterile
inflammation
have
not
yet
been
detailed.
Necroinflammation
associated
with
release
damage-associated
molecular
patterns
(DAMP)
from
dying
cells.
In
this
review,
we
present
that
distinct
mechanisms
during
apoptosis,
necroptosis,
pyroptosis,
ferroptosis
lead
DAMPs
their
suppressors,
SAMPs.
We
summarize
currently
available
data
on
how
cell
death
pathways
released
SAMPs
direct
differentiation
ILC
Understanding
necroinflammation
can
be
crucial
in
developing
strategies
for
treatment
inflammatory
diseases
caused
processes.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Feb. 14, 2023
Cold-inducible
RNA-binding
protein
(CIRP)
is
an
intracellular
stress-response
and
a
type
of
damage-associated
molecular
pattern
(DAMP)
that
responds
to
various
stress
stimulus
by
altering
its
expression
mRNA
stability.
Upon
exposure
ultraviolet
(UV)
light
or
low
temperature,
CIRP
get
translocated
from
the
nucleus
cytoplasm
through
methylation
modification
stored
in
granules
(SG).
During
exosome
biogenesis,
which
involves
formation
endosomes
cell
membrane
endocytosis,
also
gets
packaged
within
along
with
DNA,
RNA
other
proteins.
Subsequently,
intraluminal
vesicles
(ILVs)
are
formed
following
inward
budding
endosomal
membrane,
turning
into
multi-vesicle
bodies
(MVBs).
Finally,
MVBs
fuse
form
exosomes.
As
result,
can
be
secreted
out
cells
lysosomal
pathway
as
Extracellular
(eCIRP).
(eCIRP)
implicated
conditions,
including
sepsis,
ischemia-reperfusion
damage,
lung
injury,
neuroinflammation,
release
In
addition,
interacts
TLR4,
TREM-1,
IL-6R,
therefore
involved
triggering
immune
inflammatory
responses.
Accordingly,
eCIRP
has
been
studied
potential
novel
targets
for
disease
therapy.
C23
M3,
polypeptides
oppose
binding
receptors,
beneficial
numerous
illnesses.
Some
natural
molecules
such
Luteolin
Emodin
antagonize
CIRP,
play
roles
similar
responses
inhibit
macrophage-mediated
inflammation.
This
review
aims
provide
better
understanding
on
translocation
secretion
extracellular
space
mechanisms
inhibitory
diverse