Human
labour
is
shown
to
be
an
inflammatory
process,
which
involves
a
marked
leukocyte
infiltrate
into
myometrium
during
labour.
My
study
focused
on
the
role
of
chemokines,
key
mediators
of
leukocyte
trafficking,
in
labour.
Previous
gene
array
data
obtained
from
human
labouring
myometrium
showed
that
the
mRNA
expression
of
the
following
chemokines
was
increased
in
term
labouring
myometrium,
CCL2,
CCL20,
CXCL1,
CXCL5,
CXCL8.
I
decided
to
focus
on
myometrial
expression
of
these
chemokines
and
also
to
include
CCL5,
another
important
chemokine.
My
data
confirmed
that
the
expression
of
human
myometrial
chemokines
was
increased
in
labour
and
that
their
expression
was
up
regulated
by
cytokines
and
mechanical
stretch
via
NFKB
and
MAPK,
but
decreased
by
prostaglandins
and
oxytocin
via
PLC.
I
also
studied
the
expression
of
myometrial
chemokine
receptors,
which
may
mediate
some
of
the
effects
of
chemokines
on
myometrial
function
and/or
act
as
decoys,
minimising
the
effects
of
locally
produced
chemokines.
I
found
that
the
expression
of
the
chemokine
receptors
decreased
with
the
onset
of
labour,
mainly
through
the
action
of
prostaglandins
and
oxytocin.
I
then
used
the
established
model
of
LPS-­‐induced
preterm
labour
(PTL)
in
the
mouse
and
found
that
chemokines
and
cytokines
both
increased
in
the
myometrium
and
placenta.
CCL2
is
consistently
increased
with
human
labour
and
has
been
shown
to
be
important
in
rodent
parturition
too.
I
therefore
studied
the
impact
of
LPS
in
the
CCR2
(the
main
receptor
for
CCL2)
knockout
mouse.
There
was
less
inflammation
in
both
the
myometrium
and
placenta
and
a
better
pup
survival
rate
in
the
CCR2-/-
mouse.
However,
the
PTL
was
not
delayed,
suggesting
that
CCR2
is
not
essential
for
the
induction
of
PTL
labour
by
LPS
in
the
mouse.
I
then
turned
my
attention
to
CCL20,
which
acts
only
via
CCR6.
It
is
known
to
drive
dendritic
cell
recruitment
and
I
found
that
its
expression
was
increased
with
labour,
while
that
of
its
receptor
was
reduced.
Functionally,
I
found
that
CCL20
up-regulated
the
myometrial
expression
of
chemokines.
Next
I
used
the
LPS-induced
preterm
labour
model
in
the
mouse
and
found
that
CCR6
knockout
delayed
LPS-induced
preterm
delivery
and
improved
pup
survival.
These
findings
were
associated
with
much
lower
inflammation
in
myometrium
and
plasma.
These
data
suggest
that
CCR6
could
be
a
therapeutic
target
in
the
management
of
PTL.
Chemokines
play
an
important
role
both
in
the
induction
of
term
labour
and
in
infection
induced
PTL.
Chemokine
inhibitors
may
delay
the
onset
of
PTL
and
improve
the
fetal
outcome.