http://stroke.ahajournals.org/content/47/Suppl_1/ATP264.short
+ Author Affiliations
Abstract
Background and Purpose:
ST2, a member of the interleukin 1 receptor family, and its ligand
interleukin 33 (IL-33) play critical roles in immune regulation
and inflammatory responses. The engagement of
ST2 has been shown to reduce myocardial infarction and preserve heart
function.
Recent study documented an increase in blood ST2
expression after stroke. The exact roles of ST2 in the ischemic brain
injury,
however, are not explored.
Methods: C57/BL6 wild
type and ST2 knockout mice were subjected to 60-minute transient
cerebral ischemia (tMCAO). The expression of
ST2 and IL-33 in the ischemic brain was measured
at different time points after tMCAO using RT-PCR. Brain infarct was
quantified
using TTC staining and MAP2 immunostaing.
Neurobehavioral tests were performed up to 14 days after tMCAO.
Differences of immune
cell components in blood, spleen, bone marrow
and brain between wild type and ST2 knockout mice were assessed by flow
cytometry
analysis. For experiments with ST2 activation,
IL-33 was injected intraperitoneally(i.p.) or intracerebroventricularly
(i.c.v.)
into wide type mice right after the induction of
tMCAO.
Results: In wild type
mice, the mRNA expression of ST2 in the ischemic brainexhibited a
delayed elevation 7d after tMCAO, while the
mRNA expression of IL-33 was transiently
increased 1d after tMCAO. The deficiency of ST2 resulted in enlarged
infarct volume
3d after tMCAO and aggravated neurological
deficits lasted out to 14d. The worsened stroke outcome was accompanied
by dramatic
changes in the number of Th1, Th2 and regulatory
T cells in the spleen, bone marrow and brain. Further study showed that
either
i.p. or i.c.v. injection of IL-33 at the time of
reperfusion attenuated the severity of brain infarct in wide type mice,
suggesting
that both systemic and central activation of ST2
could protect against acute ischemic brain injury.
Conclusions: ST2/IL-33
signaling plays an essential role in restricting acute ischemic brain
injury. Such protective effect of ST2/IL-33
involves both immune regulation in the
peripheral immune system and a direct protection within the central
nervous system.
Our study may provide a new therapeutic target
for stroke treatment.
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