Chen Keqiang, Huang Jian, Gong Wanghua, Iribarren Pablo, Dunlop Nancy M, Wang Ji Ming
Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Int Immunopharmacol. 2007 Oct;7(10):1271-85. doi: 10.1016/j.intimp.2007.05.016. Epub 2007 Jun 21.
Members of the Toll-like receptor (TLR) family play key roles in both innate and adaptive immune responses. TLR proteins enable host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharides, viral RNA, CPG-containing DNA, and flagellin, among others. TLRs are also apparently able to mediate responses to host molecules, including one defensin, ROS, HMGB1 (high-mobility group box protein 1), surfactant protein A, fibrinogen, breakdown products of tissue matrix, heat shock proteins (hsp) and eosinophil-derived neurotoxin (EDN). Thus, TLR are involved in the development of many pathological conditions including infectious diseases, tissue damage, autoimmune and neurodegenerative diseases and cancer. In this review, the contribution of TLRs to diseases of the central nervous system (CNS), lung, gastrointestinal tract, kidney and skin as well as cancer is evaluated. We hope to provide new insight into the pathogenesis and progression of diseases and more importantly, into the potential for TLRs as targets of therapeutics.
Toll样受体(TLR)家族成员在先天性和适应性免疫反应中均发挥关键作用。TLR蛋白使宿主能够识别大量病原体相关分子模式,如细菌脂多糖、病毒RNA、含胞嘧啶-磷酸-鸟嘌呤的DNA以及鞭毛蛋白等。TLR显然还能够介导对宿主分子的反应,包括一种防御素、活性氧、高迁移率族蛋白B1(HMGB1)、表面活性蛋白A、纤维蛋白原、组织基质降解产物、热休克蛋白(hsp)和嗜酸性粒细胞衍生神经毒素(EDN)。因此,TLR参与了许多病理状况的发生发展,包括传染病、组织损伤、自身免疫性疾病、神经退行性疾病和癌症。在本综述中,评估了TLR在中枢神经系统(CNS)、肺、胃肠道、肾脏和皮肤疾病以及癌症中的作用。我们希望为疾病的发病机制和进展提供新的见解,更重要的是,为TLR作为治疗靶点的潜力提供新的见解。