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. 2010:2010:142458.
doi: 10.1155/2010/142458. Epub 2010 Sep 29.

Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage

Yu Zhou  1 , Kun-Lin Xiong, Sen Lin, Qi Zhong, Feng-Lin Lu, Hong Liang, Jing-Cheng Li, Jing-Zhou Wang, Qing-Wu Yang
Affiliations

Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage

Yu Zhou et al. Mediators Inflamm. 2010.

Abstract

High-mobility group protein box-1 (HMGB1) is a proinflammatory involved in many inflammatory diseases. However, its roles in intracerebral hemorrhage (ICH) remain unknown. The purpose of this study was to examine the correlation between changes in serum levels of HMGB1 following acute ICH and the severity of stroke as well as the underlying mechanism. Changes in serum levels of HMGB1 in 60 consecutive patients with primary hemispheric ICH within 12 hours of onset of symptoms were determined. The correlation of HMGB1 with disease severity, IL-6, and TNF-α was analyzed. Changes in HMGB1 levels were detected with ELISA and Western blot. Compared with normal controls, patients with ICH had markedly elevated levels of HMGB1, which was significantly correlated with the levels of IL-6 and TNF-α, NIHSS score at the 10th day, and mRS score at 3 months. In comparison with the control group, the levels of HMGB1 in the perihematomal tissue in mice with ICH increased dramatically, peaked at 72 hours, and decreased at 5 days. Meanwhile, heme could stimulate cultured microglia to release large amounts of HMGB1 whereas Fe(2+/3+) ions failed to stimulate HMGB1 production from microglia. Our findings suggest that HMGB1 may play an essential role in the ICH-caused inflammatory injury.

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Figures

Figure 1
Figure 1
Serum level of HMGB1 increased significantly in patients with acute ICH. Data are presented as mean ± standard deviation. (a) ELISA assay of the changes of HMGB1 serum levels in patients. (b) A representative picture of Western blot assay showing the changes of HMGB1 serum levels in patients. GAPDH was chosen as the internal control. The changes of HMGB1 were expressed as the ratio of the optical density values of HMGB1 band to the optical density values of GAPDH band. **versus control; P < .01; ##versus good outcome group; P < .01.
Figure 2
Figure 2
The level of HMGB1 increased significantly in the perihematomal tissue of ICH mice. Data are expressed as mean ± standard deviation. (a) ELISA assay of the changes of HMGB1 levels in the perihematomal tissue of ICH mice. (b) A representative picture of Western blot assay showing the changes of HMGB1 levels in the perihematomal tissue of mice. GAPDH was chosen as the internal control. The changes of HMGB1 were expressed as the ratio of the optical density values of HMGB1 band to the optical density values of GAPDH band. n = 15. **versus control; P < .01; ##versus 72 hours; P < .01.
Figure 3
Figure 3
Heme could stimulate the secretion of HMGB1 by cultured microglia. Data are expressed as mean ± standard deviation, n = 6. (a) Microglia were cultured with various concentrations of heme (0 μM, 10 μM, 20 μM, and 30 μM) for 24 hours. Thereafter, the culture medium was replaced, and the cells were further cultured for 12 hours before collection of the supernatant for ELISA determination of HMGB1 levels. **versus 0 μM; P < .01; ##versus 10 μM, 20 μM; P < .01. (b) Microglia were treated with 30 μM of heme for various lengths of time (0 h, 4 h, 8 h, 24 h, and 48 h). Thereafter, the culture medium was replaced, and the cells were further cultured for another 12 hours before collection of the supernatant for ELISA determination of HMGB1 levels. **versus 0 h; P < .01; ##versus 4 h, 8 h, or 24 h; P < .01. (c) Microglia were treated with 30 μM of heme, 30 μM of FeCl3, or 30 μM of FeSO4 for 24 hours. Thereafter, the culture medium was replaced, and the cells were further cultured for another 12 hours before collection of the supernatant for ELISA determination of HMGB1 levels. **versus control; P < .01.
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