Eleftheriadis Theodoros, Pissas Georgios, Liakopoulos Vassilios, Stefanidis Ioannis, Lawson Brian R
Department of Nephrology, Medical School, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110 Larissa, Greece.
Inflamm Allergy Drug Targets. 2012 Dec;11(6):464-77. doi: 10.2174/187152812803589994.
Toll-like receptors (TLRs) are the first identified and best studied family of pattern recognition receptors. Expressed in immunocytes, TLRs initiate innate immune responses and concurrently shape the subsequent adaptive immune response. They are sensors of both pathogens, through the exogenous pathogen-associated molecular patterns (PAMPs), and tissue injury, through the endogenous danger-associated molecular patterns (DAMPs). In addition to immunocytes, TLRs are widely distributed in various cell types, including renal cells where they contribute significantly to various pathologies. In particular, many experimental and emerging clinical data indicate that TLRs are involved in the pathogenesis of urinary tract infections, sepsis-induced renal failure, kidney ischemia/reperfusion injury, idiopathic or systemic autoimmunity-induced glomerulonephritis and ultimately is renal fibrosis, which leads to end-stage renal disease. This review summarizes the present data about the important role TLRs play in the above kidney diseases focusing on the specific role of PAMPs versus DAMPs and of local versus systemic TLR activation.
Toll样受体(TLRs)是最早被鉴定且研究最为深入的模式识别受体家族。TLRs表达于免疫细胞中,启动固有免疫反应,并同时塑造随后的适应性免疫反应。它们既是病原体的传感器,通过外源性病原体相关分子模式(PAMPs)发挥作用,也是组织损伤的传感器,通过内源性危险相关分子模式(DAMPs)发挥作用。除免疫细胞外,TLRs广泛分布于各种细胞类型中,包括肾细胞,在肾细胞中它们对各种病理过程有重要影响。特别是,许多实验数据和新出现的临床数据表明,TLRs参与尿路感染、脓毒症诱导的肾衰竭、肾脏缺血/再灌注损伤、特发性或系统性自身免疫性肾小球肾炎的发病机制,最终导致肾纤维化,进而发展为终末期肾病。本综述总结了目前关于TLRs在上述肾脏疾病中所起重要作用的数据,重点关注PAMPs与DAMPs的具体作用以及局部与全身TLR激活的作用。