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.
出处
《国际口腔医学杂志》
CAS
2014年第3期304-308,共5页
International Journal of Stomatology
基金
广东省科技计划项目(2010B060900053)
关键词
TOLL样受体
信号通路
转导抑制
炎症治疗
Toll-like receptor
signal pathway
pathway inhibition
inflammatory treatment
