PMID- 11157195
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20190727
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 32
IP  - 2
DP  - 2001 Feb
TI  - Reduction of inflammatory response in the mouse brain with adenoviral-mediated 
      transforming growth factor-ss1 expression.
PG  - 544-52
AB  - Background and Purpose-Chemokines have been shown to play an important role in 
      leukocyte and monocyte/macrophage infiltration into ischemic regions. The purpose 
      of this study is to identify whether overexpression of the active human 
      transforming growth factor-ss1 (ahTGF-ss1) can downregulate expression of 
      monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory 
      protein-1alpha (MIP-1alpha), and intercellular adhesion molecule-1 (ICAM-1) and 
      reduce ischemic brain injury. METHODS: -Overexpression of transforming growth 
      factor-ss1 (TGF-ss1) was achieved through adenoviral gene transfer. Five days 
      after adenoviral transduction, the mouse underwent 30 minutes of middle cerebral 
      artery occlusion followed by 1 to 7 days of reperfusion. TGF-ss1, MCP-1, 
      MIP-1alpha, and ICAM-1 were detected by enzyme-linked immunosorbent assay and 
      immunohistochemistry. Infarct areas and volumes were measured by cresyl violet 
      staining. RESULTS: -MCP-1 and MIP-1alpha expression is increased after middle 
      cerebral artery occlusion, and double-labeled immunostaining revealed that MCP-1 
      is colocalized with neurons and astrocytes. Viral-mediated TGF-ss1 overexpression 
      was significantly greater at measured time points, with a peak at 7 to 9 days. 
      The expression of MCP-1 and MIP-1alpha, but not ICAM-1, was reduced in the mice 
      overexpressing ahTGF-ss1 (P:<0.05). Furthermore, infarct volume was significantly 
      reduced in the mice overexpressing ahTGF-ss1 (P:<0.05). CONCLUSIONS: -This study 
      demonstrates that MCP-1 and MIP-1alpha expressed in the ischemic region may play 
      an important role in attracting inflammatory cells. The reduction of MCP-1 and 
      MIP-1alpha, but not ICAM-1, in the mice overexpressing ahTGF-ss1 suggests that 
      the neuroprotective effect of TGF-ss1 may result from the inhibition of 
      chemokines during cerebral ischemia and reperfusion.
FAU - Pang, L
AU  - Pang L
AD  - Department of Surgery, Medical School, University of Michigan, Ann Arbor, MI 
      48109-0532, USA.
FAU - Ye, W
AU  - Ye W
FAU - Che, X M
AU  - Che XM
FAU - Roessler, B J
AU  - Roessler BJ
FAU - Betz, A L
AU  - Betz AL
FAU - Yang, G Y
AU  - Yang GY
LA  - eng
GR  - NS23870/NS/NINDS NIH HHS/United States
GR  - NS35089/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Adenoviridae/genetics/*metabolism
MH  - Animals
MH  - Blood Flow Velocity
MH  - Brain/blood supply/immunology/*metabolism/virology
MH  - Brain Ischemia/immunology/*metabolism/pathology
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Disease Models, Animal
MH  - Gene Transfer Techniques
MH  - Genetic Vectors/genetics/metabolism/pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Infarction, Middle Cerebral Artery
MH  - Inflammation/drug therapy/immunology/*metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Macrophage Inflammatory Proteins/metabolism
MH  - Mice
MH  - Reperfusion
MH  - Transforming Growth Factor beta/*biosynthesis/genetics/pharmacology
MH  - Transforming Growth Factor beta1
EDAT- 2001/02/07 11:00
MHDA- 2001/06/08 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1161/01.str.32.2.544 [doi]
PST - ppublish
SO  - Stroke. 2001 Feb;32(2):544-52. doi: 10.1161/01.str.32.2.544.