Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 β

Journal of Neuroinflammation

Eleonora Aronica¹  Jan A Gorter¹  Jaap C Reijneveld⁴  Jan J Heimans⁴  Erwin A van Vliet³  Jasper Anink²  Anand Iyer²  Marjolein de Groot⁴  Emanuele Zurolo² 

[1] Epilepsy Institute in The Netherlands Foundation (Stichting Epilepsie Instellingen Nederland, SEIN), Heemstede, The Netherlands;Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, AZ 1105, The Netherlands;Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands;Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands

关键词: Brain tumors;    Astrocytes;    Interleukin-1 β;    Potassium channels;    Inflammation;    Epilepsy;   

Others  :  1160087
DOI  :  10.1186/1742-2094-9-280

 received in 2012-08-08, accepted in 2012-12-09,  发布年份 2012

【 摘 要 】

Objective

Decreased expression of inwardly rectifying potassium (Kir) channels in astrocytes and glioma cells may contribute to impaired K⁺ buffering and increased propensity for seizures. Here, we evaluated the potential effect of inflammatory molecules, such as interleukin-1β (IL-1β) on Kir4.1 mRNA and protein expression.

Methods

We investigated Kir4.1 (Kcnj10) and IL-1β mRNA expression in the temporal cortex in a rat model of temporal lobe epilepsy 24 h and 1 week after induction of status epilepticus (SE), using real-time PCR and western blot analysis. The U373 glioblastoma cell line and human fetal astrocytes were used to study the regulation of Kir4.1 expression in response to pro-inflammatory cytokines. Expression of Kir4.1 protein was also evaluated by means of immunohistochemistry in surgical specimens of patients with astrocytic tumors (n = 64), comparing the expression in tumor patients with (n = 38) and without epilepsy (n = 26).

Results

Twenty-four hours after onset of SE, Kir4.1 mRNA and protein were significantly down-regulated in temporal cortex of epileptic rats. This decrease in expression was followed by a return to control level at 1 week after SE. The transient downregulation of Kir4.1 corresponded to the time of prominent upregulation of IL-1β mRNA. Expression of Kir4.1 mRNA and protein in glial cells in culture was downregulated after exposure to IL-1β. Evaluation of Kir4.1 in tumor specimens showed a significantly lower Kir4.1 expression in the specimens of patients with epilepsy compared to patients without epilepsy. This paralleled the increased presence of activated microglial cells, as well as the increased expression of IL-1β and the cytoplasmic translocation of high mobility group box 1 (HMGB1).

Conclusions

Taken together, these findings indicate that alterations in expression of Kir4.1 occurring in epilepsy-associated lesions are possibly influenced by the local inflammatory environment and in particular by the inflammatory cytokine IL-1β.

【 授权许可】

   
2012 Zurolo et al.; licensee BioMed Central Ltd.

【 图 表 】

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