白细胞介素-1受体家族成员ST2在心肌细胞及心肌梗死中的表达与调控
Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction.
作者信息
Weinberg Ellen O, Shimpo Masahisa, De Keulenaer Gilles W, MacGillivray Catherine, Tominaga Shin-ichi, Solomon Scott D, Rouleau Jean-Lucien, Lee Richard T
机构信息
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Mass 02139, USA.
出版信息
Circulation. 2002 Dec 3;106(23):2961-6. doi: 10.1161/01.cir.0000038705.69871.d9.
Abstract
BACKGROUND
We identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes and hypothesized that ST2 participates in the acute myocardial response to stress and injury.
METHODS AND RESULTS
ST2 mRNA was induced in cardiac myocytes by mechanical strain (4.7+/-0.9-fold) and interleukin-1beta (2.0+/-0.2-fold). Promoter analysis revealed that the proximal and not the distal promoter of ST2 is responsible for transcriptional activation in cardiac myocytes by strain and interleukin-1beta. In mice subjected to coronary artery ligation, serum ST2 was transiently increased compared with unoperated controls (20.8+/-4.4 versus 0.8+/-0.8 ng/mL, P<0.05). Soluble ST2 levels were increased in the serum of human patients (N=69) 1 day after myocardial infarction and correlated positively with creatine kinase (r=0.41, P<0.001) and negatively with ejection fraction (P=0.02).
CONCLUSIONS
These data identify ST2 release in response to myocardial infarction and suggest a role for this innate immune receptor in myocardial injury.
摘要
背景
我们鉴定出一种白细胞介素-1受体家族成员ST2，它是心肌细胞中受机械牵张显著诱导的基因，并推测ST2参与心肌对应激和损伤的急性反应。
方法与结果
机械牵张（4.7±0.9倍）和白细胞介素-1β（2.0±0.2倍）可诱导心肌细胞中ST2 mRNA表达。启动子分析显示，ST2的近端而非远端启动子负责心肌细胞中由牵张和白细胞介素-1β介导的转录激活。在冠状动脉结扎的小鼠中，与未手术的对照组相比，血清ST2短暂升高（20.8±4.4对0.8±0.8 ng/mL，P<0.05）。心肌梗死后1天，人类患者（N=69）血清中可溶性ST2水平升高，且与肌酸激酶呈正相关（r=0.41，P<0.001），与射血分数呈负相关（P=0.02）。
结论
这些数据确定了心肌梗死后ST2的释放，并提示这种天然免疫受体在心肌损伤中发挥作用。
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