Yin Y, Yan Y, Jiang X, Mai J, Chen N C, Wang H, Yang X-F
Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):311-22. doi: 10.1177/039463200902200208.
To determine the expression of components in Toll-like receptors (TLRs)/Nod-like receptors (NLRs)/inflammasome/caspase-1/interleukin (IL-1)-beta pathway, we examined the expression profiles of those genes by analyzing the data from expression sequence tag cDNA cloning and sequencing. We made several important findings: firstly, among 11 tissues examined, vascular tissues and heart express fewer types of TLRs and NLRs than immune and defense tissues including blood, lymph nodes, thymus and trachea; secondly, brain, lymph nodes and thymus do not express proinflammatory cytokines IL-1beta and IL-18 constitutively, suggesting that these two cytokines need to be upregulated in the tissues; and thirdly, based on the expression data of three characterized inflammasomes (NALP1, NALP3 and IPAF inflammasome), the examined tissues can be classified into three tiers: the first tier tissues including brain, placenta, blood and thymus express inflammasome(s) in constitutive status; the second tier tissues have inflammasome(s) in nearly-ready expression status (with the requirement of upregulation of one component); the third tier tissues, like heart and bone marrow, require upregulation of at least two components in order to assemble functional inflammasomes. Our original model of three-tier expression of inflammasomes would suggest a new concept of tissue inflammation privilege, and provides an insight to the differences among tissues in initiating acute inflammation in response to stimuli.
为了确定Toll样受体(TLRs)/Nod样受体(NLRs)/炎性小体/半胱天冬酶-1/白细胞介素(IL-1)-β通路中各组分的表达情况,我们通过分析表达序列标签cDNA克隆和测序数据来检测这些基因的表达谱。我们有几个重要发现:首先,在所检测的11种组织中,与包括血液、淋巴结、胸腺和气管在内的免疫和防御组织相比,血管组织和心脏表达的TLRs和NLRs类型较少;其次,脑、淋巴结和胸腺组成型不表达促炎细胞因子IL-1β和IL-18,这表明这两种细胞因子在这些组织中需要上调表达;第三,根据三种已明确的炎性小体(NALP1、NALP3和IPAF炎性小体)的表达数据,所检测的组织可分为三层:第一层组织包括脑、胎盘、血液和胸腺,以组成型状态表达炎性小体;第二层组织的炎性小体处于几乎准备好表达的状态(需要上调一种组分);第三层组织,如心脏和骨髓,需要上调至少两种组分才能组装成功能性炎性小体。我们最初提出的炎性小体三层表达模型提示了一种新的组织炎症特权概念,并为不同组织在对刺激作出反应时引发急性炎症的差异提供了见解。