Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / immunology
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Cell Line
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Chemokine CCL20
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Chemokines, CC / analysis*
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Epstein-Barr Virus Infections / genetics*
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Epstein-Barr Virus Infections / immunology
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Herpesvirus 4, Human / genetics
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Herpesvirus 4, Human / immunology
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Histone Deacetylase 1
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Histone Deacetylases / immunology
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Humans
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Kidney / immunology
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Macrophage Inflammatory Proteins / analysis*
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NF-kappa B / genetics
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NF-kappa B / immunology
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Promoter Regions, Genetic / genetics
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Promoter Regions, Genetic / immunology
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RNA, Messenger / analysis
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Signal Transduction / genetics
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Signal Transduction / immunology
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Transcriptional Activation / genetics
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Transcriptional Activation / immunology
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Up-Regulation / genetics
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Up-Regulation / immunology
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Viral Matrix Proteins / genetics*
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Viral Matrix Proteins / immunology
Substances
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CCL20 protein, human
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Chemokine CCL20
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Chemokines, CC
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EBV-associated membrane antigen, Epstein-Barr virus
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Macrophage Inflammatory Proteins
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NF-kappa B
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Neoplasm Proteins
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RNA, Messenger
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Viral Matrix Proteins
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases