Fasciano Stephen, Li Liwu
Department of Biology, Institute for Biomedical and Public Health Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Curr Med Chem. 2006;13(12):1389-95. doi: 10.2174/092986706776872916.
Human innate immunity plays a pivotal role in host defense against various microbial challenges. Mediated by a family of Toll-like-receptors (TLR) and associated intracellular downstream signaling molecules, human innate immunity can specifically recognize diverse microbial products and many other non-microbial environmental cues. Beyond its role of providing first line of defense, activation of innate immunity signaling can lead to expression of diverse pro- and anti- inflammatory mediators, which are critical for regulating various cell and tissue metabolism. Alteration in innate immunity signaling may therefore lead to infection and inflammatory diseases such as atherosclerosis, diabetes, and cancer. TLR receptors as well as intracellular signaling proteins can serve as therapeutic targets for treating various inflammatory diseases. Several synthetic ligands of TLR receptors such as lipid A analogs, poly(I:C), loxoribine, oligodeoxynucleotides have been shown to be effective in regulating innate immune response. This review discusses the potential, challenge, and recent progress of developing synthetic as well as naturally occurring TLR ligands in regulating innate immunity and treating inflammatory diseases.
人类先天免疫在宿主抵御各种微生物挑战中起着关键作用。由Toll样受体（TLR）家族及相关细胞内下游信号分子介导，人类先天免疫能够特异性识别多种微生物产物以及许多其他非微生物环境信号。除了提供第一道防线的作用外，先天免疫信号的激活可导致多种促炎和抗炎介质的表达，这对于调节各种细胞和组织代谢至关重要。因此，先天免疫信号的改变可能导致感染和炎症性疾病，如动脉粥样硬化、糖尿病和癌症。TLR受体以及细胞内信号蛋白可作为治疗各种炎症性疾病的治疗靶点。几种TLR受体的合成配体，如脂多糖类似物、聚肌胞苷酸、洛索立宾、寡脱氧核苷酸，已被证明在调节先天免疫反应方面有效。本文综述了开发合成以及天然存在的TLR配体在调节先天免疫和治疗炎症性疾病方面的潜力、挑战和最新进展。
