Wang Guo-bing, Li Cheng-rong, Zu Ying, Yuan Xiong-wei
Department of Molecular Immunology, Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
Zhonghua Er Ke Za Zhi. 2006 May;44(5):333-6.
A great deal of clinical evidence and epidemiologic data suggest that Kawasaki disease (KD) is correlated with an acute regulating imbalance of immunology. Lots of evidences in the past suggested that nuclear transcription factor-kappaB and preinflammation factors were up-regulated significantly in patients with KD. But the causative factors are still unknown. Toll-like receptors (TLRs) is a type I trans-membrane protein which could recognize ligands of pathogen microbes, activate the nuclear transcription factor-kappaB and promote gene transcription of pre-inflammation factors and co-stimulatory molecules on cell surface. Aberrant activation of signal pathway of TLRs could interfere with autoimmune tolerance and cause autoimmune diseases. The study was designed to investigate the role of signal transduction of TLRs on immunological pathogenesis of KD.
Sixteen children with KD and 16 age-matched health children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs 1 - 10, MD-2, MyD88, IL-1beta, IL-6 and IL-8 mRNA expressions in peripheral blood mononuclear cells, and expressions of TLRs 2, 4 and co-stimulatory molecules such as CD80 and CD86 in monocyte/macrophage were analyzed by flow cytometry.
(1) Compared with control group, the protein and mRNA levels of TLR4 in KD group were up-regulated significantly [(Real-time PCR: 325.22 +/- 50.34 vs. 2.20 +/- 0.23, P < 0.01); (flow cytometry: 15.96% +/- 5.94% vs. 3.21% +/- 0.62%, P < 0.01)], the difference being not significant as to other TLRs. (2) Transcriptional levels of MD-2 and Myd88 were significantly up-regulated in acute phase of KD (P < 0.01), and down-regulated after the treatment with intravenous gamma globulin therapy. (3) Expressions of co-stimulatory molecules and cytokines in monocyte/macrophage during acute phase of KD were higher than those of control group (P < 0.01).
Expressions of TLRs 4, MD-2 and Myd88 were up-regulated during acute phase in KD, suggesting that aberrant activation of TLRs 4 might be one of the initiating factors of immune aberrance in KD.
大量临床证据和流行病学数据表明，川崎病（KD）与急性免疫调节失衡相关。过去许多证据表明，KD患者体内核转录因子-κB和前炎症因子显著上调。但其致病因素仍不清楚。Toll样受体（TLRs）是一种I型跨膜蛋白，可识别病原微生物的配体，激活核转录因子-κB并促进前炎症因子和细胞表面共刺激分子的基因转录。TLRs信号通路的异常激活可干扰自身免疫耐受并导致自身免疫性疾病。本研究旨在探讨TLRs信号转导在KD免疫发病机制中的作用。
研究16例KD患儿和16例年龄匹配的健康儿童。采用逆转录聚合酶链反应（RT-PCR）和实时定量PCR评估外周血单个核细胞中TLRs 1 - 10、MD-2、MyD88、IL-1β、IL-6和IL-8 mRNA的表达水平，并通过流式细胞术分析单核细胞/巨噬细胞中TLRs 2、4及共刺激分子如CD80和CD86的表达。
（1）与对照组相比，KD组TLR4的蛋白和mRNA水平显著上调[（实时定量PCR：325.22±50.34 vs. 2.20±0.23，P<0.01）；（流式细胞术：15.96%±5.94% vs. 3.21%±0.62%，P<0.01）]，其他TLRs差异不显著。（2）KD急性期MD-2和Myd88的转录水平显著上调（P<0.01），静脉注射丙种球蛋白治疗后下调。（3）KD急性期单核细胞/巨噬细胞中共刺激分子和细胞因子的表达高于对照组（P<0.01）。
KD急性期TLR4、MD-2和Myd88表达上调，提示TLR4的异常激活可能是KD免疫异常的起始因素之一。
