Activation of nuclear factor κB in cerebral arteriovenous malformations.
BACKGROUND
Cerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations, but rather are dynamically changing pathologies. It is well-known from clinical situations that these AVMs can enlarge or shrink. Nuclear factor κB (NF-κB) is a nuclear transcription factor that regulates a number of physiological processes, such as inflammation, apoptosis, and cellular growth.


OBJECTIVE
To analyze phosphorylation of NF-κB and related molecules in cerebral AVM specimens.


METHODS
We examined 19 specimens of cerebral AVMs from 18 patients. Immunohistochemical analysis was performed using an NF-κB p65 (C22B4) rabbit monoclonal antibody, the phosphorylated form of NF-κB (PNF-κB) p65 (Ser276) rabbit antibody, and an IκBα mouse monoclonal antibody.


RESULTS
Expression of NF-κB was mainly confined to the endothelial lining and the infiltrating inflammatory cells in the perivascular regions. PNF-κB showed the highest level of expression in both endothelial cells and perivascular infiltrating cells. PNF-κB was intensely expressed in the endothelium and perivascular infiltrating cells of 15 specimens (78.9%). NF-κB and IκB were also expressed in endothelial cells and perivascular infiltrating inflammatory cells, but at lower levels than PNF-κB. Immunohistochemical studies revealed that PNF-κB was mainly concentrated in the nuclei of endothelial and infiltrating inflammatory cells. On the contrary, expression of both NF-κB and IκB was mainly concentrated in the cytoplasm of endothelial and inflammatory cells.


CONCLUSIONS
We detected activation of NF-κB in the endothelium and perivascular infiltrating inflammatory cells within the cerebral AVM nidus, suggesting a role in the pathophysiology of cerebral AVM.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Mohamed Mostafa
MM
Aziz
Yasushi
Y
Takagi
Nobuo
N
Hashimoto
Susumu
S
Miyamoto
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000201:enzymology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000201:enzymology* / Q000473:pathology*; D017254:Leukemic Infiltration / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D055815:Young Adult
D016328:NF-kappa B; D012694:Serine