PMID- 11376856
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 90
IP  - 1
DP  - 2001 May 20
TI  - Attenuation of hypoxia-ischemia-induced monocyte chemoattractant protein-1 
      expression in brain of neonatal mice deficient in interleukin-1 converting 
      enzyme.
PG  - 57-67
AB  - Interleukin-1beta (IL-1beta) upregulates expression of the chemokine monocyte 
      chemoattractant protein-1 (MCP-1) in many experimental models. In neonatal rodent 
      brain, hypoxia-ischemia rapidly stimulates expression of this chemokine, although 
      the role of IL-1beta in regulating this response is unknown. Interleukin-1 
      converting enzyme (ICE) is a cysteine protease that cleaves inactive pro-IL-1beta 
      to generate mature IL-1beta. Neonatal mice with a homozygous deletion of ICE (ICE 
      -/-) are resistant to moderate, but not to severe cerebral hypoxic-ischemic 
      insults, relative to their wild-type controls. We hypothesized that their 
      resistance to moderate hypoxic-ischemic insults is mediated by suppression of the 
      acute inflammatory response to brain injury in the absence of IL-1beta, and that 
      hypoxia-ischemia induced MCP-1 expression would be attenuated in ICE -/- animals. 
      To test this hypothesis, paired litters of 9-10-day-old ICE -/- and wild-type 
      mice underwent right carotid ligation, followed by 40, 70 or 120 min exposure to 
      10% O2 and ischemia-induced changes in MCP-1 mRNA and protein were compared, 
      using a semi-quantitative reverse-transcription polymerase chain reaction assay 
      and an ELISA, respectively. With a lesioning protocol that elicits minimal injury 
      in wild-types (ligation+40 min 10% O2), there was an attenuation of 
      hypoxia-ischemia-induced MCP-1 production at 8 h post-hypoxia; in contrast, in 
      animals that underwent longer periods of hypoxia-ischemia the magnitude of 
      injury-induced induced MCP-1 production did not differ between wild-type and ICE 
      -/- animals. These results demonstrate both that the acute inflammatory response 
      to hypoxia-ischemia is attenuated in ICE -/- animals, and also that 
      hypoxic-ischemic brain injury stimulates MCP-1 expression even in the absence of 
      IL-1beta activity.
FAU - Xu, H
AU  - Xu H
AD  - Department of Pediatrics, University of Michigan, Rm. 8301 MSRB3, Box 0646, 1150 
      W. Medical Center Dr., Ann Arbor, MI 48109-0646, USA.
FAU - Barks, J D
AU  - Barks JD
FAU - Schielke, G P
AU  - Schielke GP
FAU - Silverstein, F S
AU  - Silverstein FS
LA  - eng
GR  - 35059/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis
MH  - Asphyxia Neonatorum/metabolism
MH  - Brain/metabolism/pathology
MH  - Carotid Arteries
MH  - Caspase 1/*deficiency/genetics/physiology
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/genetics/*metabolism/pathology
MH  - Infant, Newborn
MH  - Inflammation
MH  - Interleukin-1/physiology
MH  - Ligation
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*biosynthesis/genetics
EDAT- 2001/05/30 10:00
MHDA- 2001/08/24 10:01
CRDT- 2001/05/30 10:00
PHST- 2001/05/30 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/05/30 10:00 [entrez]
AID - S0169328X01000870 [pii]
AID - 10.1016/s0169-328x(01)00087-0 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2001 May 20;90(1):57-67. doi: 
      10.1016/s0169-328x(01)00087-0.