Clinic of Anesthesiology, Intensive Care Medicine, and Pain Management, JW Goethe University, Frankfurt, Germany.
Crit Care Med. 2010 Mar;38(3):903-9. doi: 10.1097/CCM.0b013e3181ce50e6.
To test whether preconditioning with a toll-like receptor (TLR) 2 agonist protects against myocardial ischemia and reperfusion by interfering with chemokine CXCL1 release from cardiomyocytes.
C3H mice were challenged with vehicle or synthetic TLR2 agonist Pam3Cys-Ser-Lys4 (Pam3CSK4; 1 mg/kg) 24 hrs before myocardial ischemia (20 mins) and reperfusion (2 hrs or 24 hrs). Infarct size, troponin T release, and leukocyte recruitment were quantified. In murine cardiomyocytes (HL-1), we studied the expression/activation profile of TLR2 in response to stimulation with Pam3CSK4 (0.01-1 mg/mL). Furthermore, we studied the chemokine ligand 1 (CXCL1) response to Pam3CSK4 and ischemia/reperfusion in vivo and in vitro.
University hospital research laboratory.
Anesthetized male mice and murine cardiomyocytes.
Preconditioning by Pam3CSK4 reduced infarct size and troponin T release. This was accompanied by a decreased recruitment of leukocytes into the ischemic area and an improved cardiac function. In HL-1 cells, TLR2 activation amplified the expression of the receptor in a time-dependent manner and led to CXCL1 release in a concentration-dependent manner. Preconditioning by Pam3CSK4 impaired CXCL1 release in response to a second inflammatory stimulus in vivo and in vitro.
Preconditioning by TLR2 agonist Pam3CSK4 reduces myocardial infarct size after myocardial ischemia/reperfusion. One of the mechanisms involved is a diminished chemokine release from cardiomyocytes, which subsequently limits leukocyte infiltration.
通过干扰心肌细胞趋化因子 CXCL1 的释放，检测 Toll 样受体（TLR）2 激动剂预处理是否可以预防心肌缺血再灌注损伤。
在心肌缺血（20 分钟）和再灌注（2 小时或 24 小时）前 24 小时，C3H 小鼠用载体或合成 TLR2 激动剂 Pam3Cys-Ser-Lys4（Pam3CSK4；1mg/kg）处理。量化梗死面积、肌钙蛋白 T 释放和白细胞募集。在鼠心肌细胞（HL-1）中，我们研究了 TLR2 在受到 Pam3CSK4（0.01-1mg/mL）刺激时的表达/激活谱。此外，我们研究了趋化因子配体 1（CXCL1）对 Pam3CSK4 的反应以及体内和体外的缺血/再灌注。
大学医院研究实验室。
麻醉雄性小鼠和鼠心肌细胞。
Pam3CSK4 预处理可减少梗死面积和肌钙蛋白 T 释放。这伴随着缺血区白细胞募集的减少和心脏功能的改善。在 HL-1 细胞中，TLR2 激活以时间依赖性方式放大受体的表达，并以浓度依赖性方式导致 CXCL1 的释放。Pam3CSK4 预处理可损害体内和体外对第二次炎症刺激的 CXCL1 释放。
TLR2 激动剂 Pam3CSK4 预处理可减少心肌缺血再灌注后的心肌梗死面积。涉及的机制之一是心肌细胞趋化因子释放减少，从而限制白细胞浸润。
