Okudaira Taeko, Yamamoto Kazuo, Kawakami Hirochika, Uchihara Jun-Nosuke, Tomita Mariko, Masuda Masato, Matsuda Takehiro, Sairenji Takeshi, Iha Hidekatsu, Jeang Kuan-Teh, Matsuyama Toshifumi, Takasu Nobuyuki, Mori Naoki
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Br J Haematol. 2006 Feb;132(3):293-302. doi: 10.1111/j.1365-2141.2005.05877.x.
CCL20 is expected to play a crucial role in the initiation of immune responses and tumour growth. However, expression of CCL20 in Epstein-Barr virus (EBV)-associated diseases has not been studied. We examined the contribution of EBV infection and EBV-encoded latent membrane protein (LMP)-1 to CCL20 expression. EBV infection and LMP-1 induced CCL20 mRNA expression in the EBV-negative Burkitt lymphoma (BL) cell lines and the embryonic kidney cell line. Histone deacetylase inhibitor-stimulated endogenous LMP-1 also induced CCL20 expression in an EBV-positive BL cell line. Analysis of the CCL20 promoter showed that it was activated by LMP-1 C-terminal activation region (CTAR)-1 and CTAR-2. Co-expression of IkappaB alpha, IkappaB beta, IkappaB kinase (IKK)alpha, IKKbeta, IKKgamma, nuclear factor (NF)-kappaB-inducing kinase and tumour necrosis factor receptor-associated factor 2 dominant-negative constructs with LMP-1 inhibited the activation of the CCL20 promoter by LMP-1, suggesting that LMP-1 induces CCL20 via NF-kappaB signalling. The requirement for the NF-kappaB-binding site in the CCL20 promoter in LMP-1 responsiveness was established. Our results indicate that activation of the NF-kappaB pathway by LMP-1 is required for the activation of CCL20 expression.
CCL20有望在免疫反应启动和肿瘤生长过程中发挥关键作用。然而，CCL20在爱泼斯坦-巴尔病毒（EBV）相关疾病中的表达尚未得到研究。我们研究了EBV感染及EBV编码的潜伏膜蛋白（LMP）-1对CCL20表达的影响。EBV感染和LMP-1可诱导EBV阴性的伯基特淋巴瘤（BL）细胞系及胚胎肾细胞系中CCL20 mRNA的表达。组蛋白去乙酰化酶抑制剂刺激内源性LMP-1也可在EBV阳性的BL细胞系中诱导CCL20表达。对CCL20启动子的分析表明，它被LMP-1 C末端激活区域（CTAR）-1和CTAR-2激活。将IkappaBα、IkappaBβ、IkappaB激酶（IKK）α、IKKβ、IKKγ、核因子（NF）-κB诱导激酶及肿瘤坏死因子受体相关因子2的显性阴性构建体与LMP-1共表达，可抑制LMP-1对CCL20启动子的激活，这表明LMP-1通过NF-κB信号通路诱导CCL20表达。确定了CCL20启动子中NF-κB结合位点在LMP-1反应性中的必要性。我们的结果表明，LMP-1激活NF-κB信号通路是激活CCL20表达所必需的。
