LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium
LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium
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DOI：
10.1369/jhc.7a7299.2007
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Yoshida, Shigemitsu
中科院分区：
文献类型：
--
作者：
Sawa, Yoshihiko;Ueki, Takeshi;Yoshida, Shigemitsu
我们以前曾报道过TLR 4在人肠淋巴管中的表达。在本研究中，微阵列分析显示了TLR 4、MD-2、CD 14、MyD 88、TIRAP、TRAM、IRAK 1和TRAF 6基因在培养的人新生儿真皮淋巴微血管内皮细胞（LEC）中的表达。实时荧光定量PCR分析显示，LPS刺激后LEC表达IL-6、IL-8、VCAM-1和ICAM-1基因。LPS诱导的LEC中IL-6、IL-8、VCAM-1和ICAM-1的产生被TLR 4特异性小干扰RNA的引入以及抗TLR 4、诺贝尔碱和CAPE预处理所抑制。这些发现表明LEC具有TLR 4介导的LPS识别机制，该机制至少涉及NF-κ B的活化，导致IL-6、IL-8、VCAM-1和ICAM-1的表达增加。LPS对LEC中基因表达的影响以及Nobilipine和CAPE预处理对蛋白质产生的抑制作用在IL-6和VCAM-1中均大于IL-8和ICAM-1。NF-κ B和AP-1依赖的信号转导途径可能对LEC中IL-6和VCAM-1的表达比IL-8和ICAM-1更重要。
We have previously reported the TLR4 expression inhuman intestinal lymphatic vessels. In the study here, microarray analysis showed the expression of the TLR4, MD-2, CD14, MyD88, TIRAP, TRAM, IRAK1, and TRAF6 genes in cultured human neonatal dermal lymphatic microvascular endothelial cells (LEC). The microarray analysis also showed that LEC expressed genes of IL-6, IL-8, VCAM-1, and ICAM-1, and the real-time quantitative PCR analysis showed that mRNA production was increased by lipopolysaccharide (LPS). The LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 production in LEC was suppressed by the introduction of TLR4-specific small interfering RNA, and also by anti-TLR4, nobiletin, and CAPE pretreatment. These findings suggest that LEC has TLR4-mediated LPS recognition mechanisms that involve at least activation of NF-kappa B, resulting in increased expression of IL-6, IL-8, VCAM-1, and ICAM-1. Both the LPS effect on the gene expression and also the suppression by nobiletin and CAPE pretreatment on the protein production were larger in IL-6 and in VCAM-1 than in IL-8 and in ICAM-1 in LEC. The signal transduction of NF-kappa B and AP-1-dependent pathway may be more critical for the expression of IL-6 and VCAM-1 than that of IL-8 and ICAM-1 in LEC.