Transactivation of CCL20 gene by Epstein-Barr virus latent membrane protein 1.
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.
Okudaira
Taeko
T
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Yamamoto
Kazuo
K
Kawakami
Hirochika
H
Uchihara
Jun-Nosuke
JN
Tomita
Mariko
M
Masuda
Masato
M
Matsuda
Takehiro
T
Sairenji
Takeshi
T
Iha
Hidekatsu
H
Jeang
Kuan-Teh
KT
Matsuyama
Toshifumi
T
Takasu
Nobuyuki
N
Mori
Naoki
N
D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000276:immunology
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases