High expression level of interleukin-6 led to elevated hemorrhagic risk of cerebral arteriovenous malformations

Abstract

To explore the mechanistic roles of interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) in cerebral arteriovenous malformation (AVM). A total of 31 AVM patients were admitted into Beijing Tiantan Hospital from October 1, 2010 to October 1, 2011, including 14 ruptured and 17 non-ruptured ones. Tissue samples were obtained from all 31 patients and 30 epileptics undergoing temporal lobectomy. The blood samples were obtained from all 31 patients preoperatively and 30 healthy controls. Western blot was employed to measure transcription factors nuclear factor-κB (NF-κB), IκB and MMP-9 in tissues. And immunofluorescence was performed to measure the tissue expression of MMP-9 in each group. Gelatin zymography was used to detect the tissue expressions of activated MMP-9 and MMP-2. The blood levels of IL-6 in the ruptured group were significantly higher than those in the non-ruptured and control groups (33.2±4.8 vs 23.8±1.2 ng/L, P<0.05; 33.4±4.8 vs 15.6±1.0 ng/L, P<0.01). Protein expression in the non-ruptured group was greater than that in the normal and ruptured groups (1.20±0.35 vs 0.34±0.07; 1.20±0.35 vs 0.31±0.09, unit:molecular weight ratio of MMP-9 and β-actin), and gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured than the non-ruptured and control groups (0.98±0.07 vs 0.40±0.09; 0.98±0.07 vs 0.30±0.07, unit: ratio of MMP-9 and standard). In the ruptured group, active MMP-2 expression was significantly higher than that in the other groups. IL-6 may stimulate the transformation of MMP-9 into activated form in ruptured AVM tissues and thus lead to an elevated hemorrhage risk of AVM.