PMID- 16278864
OWN - NLM
STAT- MEDLINE
DCOM- 20060323
LR  - 20081121
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 59
IP  - 1
DP  - 2006 Jan
TI  - Interleukin-6 involvement in brain arteriovenous malformations.
PG  - 72-80
AB  - We recently reported that the GG genotype of the interleukin-6 (IL-6)-174G>C 
      promoter polymorphism is associated with clinical presentation of intracranial 
      hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we 
      investigated whether tissue IL-6 expression was associated with IL-6-174G>C 
      genotype, and whether IL-6 was linked to downstream targets involved in 
      angiogenesis and vascular instability. Our results showed that the highest IL-6 
      protein levels in brain AVM tissue were associated with IL-6-174GG genotype (GG: 
      57.7 +/- 20.2; GC: 35.6 +/- 26.6; CC: 13.9 +/- 10.2pg/mg; p = 0.001). IL-6 
      protein levels were increased in AVM tissue from patients with hemorrhagic 
      presentation compared with patients without hemorrhage (55 +/- 22 vs 40 +/- 
      27pg/mg; p = 0.038). IL-6 messenger RNA expression strongly correlated with 
      messenger RNA levels of IL-1beta, tumor necrosis factor-alpha, IL-8, matrix 
      metalloproteinase-3 (MMP-3), MMP-9, and MMP-12. We further investigated the 
      plausibility of IL-6 being an upstream cytokine responsible for initiating the 
      angiogenic cascade by cell culture and animal experiments. IL-6 induced MMP-3 and 
      MMP-9 expression and activity in mouse brain and increased proliferation and 
      migration of cerebral endothelial cells. Together, our results suggest that the 
      IL-6 genotype associated with intracranial hemorrhage modulates IL-6 expression 
      in brain AVM tissue, which is consistent with the hypothesis that inflammatory 
      processes induce angiogenic activity possibly contributory to brain AVM 
      intracranial hemorrhage.
FAU - Chen, Yongmei
AU  - Chen Y
AD  - Center for Cerebrovascular Research, University of California at San Francisco, 
      1001 Potrero Avenue, San Francisco, CA, USA.
FAU - Pawlikowska, Ludmila
AU  - Pawlikowska L
FAU - Yao, Jianhua S
AU  - Yao JS
FAU - Shen, Fanxia
AU  - Shen F
FAU - Zhai, Wenwu
AU  - Zhai W
FAU - Achrol, Achal S
AU  - Achrol AS
FAU - Lawton, Michael T
AU  - Lawton MT
FAU - Kwok, Pui-Yan
AU  - Kwok PY
FAU - Yang, Guo-Yuan
AU  - Yang GY
FAU - Young, William L
AU  - Young WL
LA  - eng
GR  - K24 NS 02091/NS/NINDS NIH HHS/United States
GR  - P01 NS 44155/NS/NINDS NIH HHS/United States
GR  - R01 NS 34949/NS/NINDS NIH HHS/United States
GR  - R01 NS 41877/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Brain/cytology/metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/cytology/metabolism
MH  - Genotype
MH  - Humans
MH  - Interleukin-6/*genetics/metabolism
MH  - Intracranial Arteriovenous Malformations/*genetics/pathology
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Mice
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Statistics as Topic
EDAT- 2005/11/10 09:00
MHDA- 2006/03/24 09:00
CRDT- 2005/11/10 09:00
PHST- 2005/11/10 09:00 [pubmed]
PHST- 2006/03/24 09:00 [medline]
PHST- 2005/11/10 09:00 [entrez]
AID - 10.1002/ana.20697 [doi]
PST - ppublish
SO  - Ann Neurol. 2006 Jan;59(1):72-80. doi: 10.1002/ana.20697.