作　　者： ; ; ;

机构地区： 南方医科大学南方医院

出　　处： 《国际口腔医学杂志》 2014年第3期304-308,共5页

摘　　要： 脂多糖(LPS)在细菌破坏细胞的过程中起着重要的作用。Toll样受体(TLR)2对LPS的识别是通过与TLR1和TLR6构成异源二聚体来完成的,TLR2识别LPS后介导的细胞内免疫反应遵循髓样分化因子(MyD)88依赖性通路。MyD88的死亡结构域募集下游的白细胞介素-1受体相关激酶1和4,肿瘤坏死因子受体相关因子6和转化生长因子-β1活化激酶等信号分子,促使核因子-κB、激活蛋白1和P38促丝裂原激活蛋白激酶活化,继而导致促炎症细胞因子相关基因转录。MyD88非依赖性通路分别募集和激活下游分子受体相互作用蛋白1或肿瘤坏死因子受体相关因子3,通过核因子-κB、激活蛋白1和干扰素调节因子3,诱导Ⅰ型干扰素的产生。CD14和MyD2是LPS与TLR4结合的关键蛋白,控制CD14或MyD2可阻止LPS和TLR4的结合,将炎症反应阻断在信号转导的上游。TLR2和TLR4对LPS的识别是引发炎症反应的关键,限制细胞对TLR2和TLR4的表达是进行炎症控制最直接有效的方法。调控TLR2和TLR4信号通路,有望给予牙周炎、炎症性肠炎、心血管疾病及和自身免疫性疾病等更有效和更安全的临床治疗。 Lipopolysaccharide（LPS） has an important function in bacteria-invading cells. Toll-like receptor（TLR） 2 can recognize LPS by forming a heterodimer with TLR1 or TLR6, which then activates cellular immune response by the myeloid differentiation factor（MyD88）-dependent pathway. The death domain of MyD88 raises downstream signaling molecules, such as interleukin（IL）-1 and IL-4 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, transforming growth factor 131 that activates nuclear factor（NF）-kB, and P38 mitogen-activated protein kinase and activator protein（AP） 1, which lead to the production of pro-inflammatory cytokines. MyD88-independent pathway reportedly activates the transcription factor interferon regulatory factor 3 and AP1, and can induce the generation of interferon 1 by activating NF-nB, tumor necrosis factor receptor-associated factor 3, and interleukin-Ⅰ receptor-1. CD14 and MyD2 are required for LPS binding to TLR4. Preventing CD14/MyD2-mediated binding of LPS to TLR4 could block inflammatory response at the outset. TLR2 and TLR4 are crucial in LPS-induced inflammation. Inhibiting the expression of TLR2 and TLR4 will be an effective and direct way to control the inflammation. A better understanding of the regulation of TLR2 and TLR4 signaling pathways will provide further support to their potential therapeutic application to periodontitis, inflammatory bowel disease, cardiovascular disease, and autoimmune diseases.

关 键 词： 样受体 信号通路 转导抑制 炎症治疗

领　　域： [生物学]