Knuefermann Pascal, Sakata Yasushi, Baker J Scott, Huang Chien-Hua, Sekiguchi Kenichi, Hardarson Hordur S, Takeuchi Osamu, Akira Shizuo, Vallejo Jesus G
Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex, USA.
Circulation. 2004 Dec 14;110(24):3693-8. doi: 10.1161/01.CIR.0000143081.13042.04. Epub 2004 Nov 29.
Staphylococcus aureus sepsis is associated with significant myocardial dysfunction. Toll-like receptor 2 (TLR2) mediates the inflammatory response to S aureus and may trigger an innate immune response in the heart. We hypothesized that a TLR2 deficiency would attenuate S aureus-induced cardiac proinflammatory mediator production and the development of cardiac dysfunction.
Wild-type and TLR2-deficient (TLR2D) mice were studied. S aureus challenge significantly increased tumor necrosis factor, interleukin-1beta, and nitric oxide expression in hearts of wild-type mice. This response was significantly blunted in TLR2D mice. Hearts from TLR2D mice had impaired S aureus-induced activation of interleukin-1 receptor-associated kinase, c-Jun NH2 terminal kinase, nuclear factor-kappaB, and activator protein-1. Moreover, hearts from TLR2D mice were protected against S aureus-induced contractile dysfunction.
These results show for the first time that TLR2 signaling contributes to the loss of myocardial contractility and cytokine production in the heart during S aureus sepsis.
金黄色葡萄球菌败血症与显著的心肌功能障碍相关。Toll样受体2（TLR2）介导对金黄色葡萄球菌的炎症反应，并可能触发心脏的固有免疫反应。我们假设TLR2缺陷会减弱金黄色葡萄球菌诱导的心脏促炎介质产生以及心脏功能障碍的发展。
对野生型和TLR2缺陷（TLR2D）小鼠进行了研究。金黄色葡萄球菌攻击显著增加了野生型小鼠心脏中肿瘤坏死因子、白细胞介素-1β和一氧化氮的表达。在TLR2D小鼠中，这种反应明显减弱。来自TLR2D小鼠的心脏在金黄色葡萄球菌诱导的白细胞介素-1受体相关激酶、c-Jun NH2末端激酶、核因子-κB和活化蛋白-1激活方面受损。此外，来自TLR2D小鼠的心脏免受金黄色葡萄球菌诱导的收缩功能障碍。
这些结果首次表明，在金黄色葡萄球菌败血症期间，TLR2信号传导导致心脏心肌收缩力丧失和细胞因子产生。
