Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice.
Interleukin-1beta (IL-1beta) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1beta affects ischemic brain are not understood. To investigate the role of IL- 1beta in regulation of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-alpha and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-alpha expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1-positive vessels in the ischemic hemisphere was reduced in ICE KO mice (P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results. The authors' results indicate that TNF-alpha expression is increased in both ICE KO and wild-type mice suggesting that TNF-alpha expression is not related to or upregulated by IL-1beta . ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1beta plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.
Yang
G Y
GY
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0532, USA.
Schielke
G P
GP
Gong
C
C
Mao
Y
Y
Ge
H L
HL
Liu
X H
XH
Betz
A L
AL
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D020170:Caspase 1