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Erschienen in:
01.10.2012 | Experimental research
RETRACTED ARTICLE: Purine anti-metabolite attenuates nuclear factor κB and related pro-inflammatory cytokines in experimental vasospasm
Erschienen in: Acta Neurochirurgica | Ausgabe 10/2012
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Background
Increased nuclear factor κB (NF-κB) bioexpression, as well as
TNF-α, IL-1β and IL-6 levels, were observed after aneurysmal
subarachnoid hemorrhage (SAH). It is of interest to investigate
the effect of 6-mercaptopurine (6-mp) on cytokines/NF-κB in this
SAH model.
Materials and methods
A rodent double-hemorrhage SAH model was employed. Serum and
cerebrospinal fluid (CSF) samples were collected to examine
IL-1, IL-6 and TNF-α levels. NF-κB subunit p65 and its inhibitor
of nuclear factor κB (IκB) were examined (by Western blot).
TNF-α was used to induce the phosphorylation of IκB in the
presence or absence of 6-mp.
Results
Nuclear NF-κB subunit p65/IκB kinase in the basilar artery was
over-expressed, and cytokines was notably increased in the SAH
groups, compared with the controls (P < 0.01). In the 6-mp SAH group, obvious
reduction was observed in NF-κB subunit p65 (nuclei) (P < 0.01). Treatment with 6-mp
significantly reduced IL-1β and TNF-α levels to those of the
healthy control. 6-Mercaptopurine also significantly increased
the level of IκB in the TNF-α-stimulated SAH rats.
Conclusions
Through inhibiting IκB bioexpression, 6-mp decreases
NF-κB-related IL-1β, IL-6, and TNF-α in the presence of SAH. The
study suggests 6-mp exerts vascular anti-inflammatory properties
through inhibiting IκB kinase and subsequently blocks
bio-activation of NF-κB and related cytokines, which may
contribute to its antivasospastic effect in animals subjected to
SAH.