Impaired adrenal stress response in Toll-like receptor 2-deficient mice
Impaired adrenal stress response in Toll-like receptor 2-deficient mice
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DOI：
10.1073/pnas.0407550101
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发表时间：
2004-11-23
影响因子：
11.1
通讯作者：
Zacharowski, K
中科院分区：
文献类型：
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作者：
Bornstein, SR;Zacharowski, P;Zacharowski, K
败血症是全球主要的健康问题之一，肾上腺类固醇释放的快速激活是这种严重疾病期间生物体第一道防线的关键事件。Toll样受体（TLR）家族在细菌感染后的早期免疫应答中是关键的，并且TLR多态性在人类中是常见的。在这里，我们证明，TLR-2缺乏症在小鼠与血浆皮质酮水平降低和肾上腺皮质组织中的显着细胞改变。TLR-2缺陷小鼠在细菌细胞壁化合物诱导的炎症应激后肾上腺皮质酮释放受损。这种缺陷似乎是由全身和肾上腺内细胞因子表达的减少介导的，包括IL-1、肿瘤坏死因子α和IL-6。我们的数据证明了先天免疫系统和内分泌应激反应之间的联系。TLR-2在肾上腺糖皮质激素调节中的关键作用需要在炎症性疾病患者中加以考虑。
Septicemia is one of the major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. The family of Toll-like receptors(TLRs) is critical in the early immune response upon bacterial infection, and TLR polymorphisms are frequent in humans. Here, we demonstrate that TLR-2 deficiency in mice is associated with reduced plasma corticosterone levels and marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release after inflammatory stress induced by bacterial cell wall compounds. This defect appears to be mediated by a decrease in systemic and intraadrenal cytokine expression, including IL-1, tumor necrosis factor alpha, and IL-6. Our data demonstrate a link between the innate immune system and the endocrine stress response. The critical role of TLR-2 in adrenal glucocorticoid regulation needs to be considered in patients with inflammatory disease.