Transactivation of CCL20 gene by Epstein-Barr virus latent membrane protein 1.

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.

• Authors: Taeko Okudaira, Kazuo Yamamoto, Hirochika Kawakami, Jun-Nosuke Uchihara, Mariko Tomita, Masato Masuda, Takehiro Matsuda, Takeshi Sairenji, Hidekatsu Iha, Kuan-Teh Jeang, Toshifumi Matsuyama, Nobuyuki Takasu, Naoki Mori
• Journal: British journal of haematology (Br J Haematol) Vol. 132 Issue 3 Pg. 293-302 (Feb 2006) ISSN: 0007-1048 [Print] England
• PMID: 16409294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• CCL20 protein, human
• Chemokine CCL20
• Chemokines, CC
• EBV-associated membrane antigen, Epstein-Barr virus
• Macrophage Inflammatory Proteins
• NF-kappa B
• Neoplasm Proteins
• RNA, Messenger
• Viral Matrix Proteins
• HDAC1 protein, human
• Histone Deacetylase 1
• Histone Deacetylases

Topics

• Burkitt Lymphoma (genetics, immunology)
• Cell Line
• Chemokine CCL20
• Chemokines, CC (analysis)
• Epstein-Barr Virus Infections (genetics, immunology)
• Gene Expression Regulation (genetics, immunology)
• Herpesvirus 4, Human (genetics, immunology)
• Histone Deacetylase 1
• Histone Deacetylases (immunology)
• Humans
• Kidney (immunology)
• Macrophage Inflammatory Proteins (analysis)
• NF-kappa B (genetics, immunology)
• Neoplasm Proteins (genetics, immunology)
• Promoter Regions, Genetic (genetics, immunology)
• RNA, Messenger (analysis)
• Signal Transduction (genetics, immunology)
• Transcriptional Activation (genetics, immunology)
• Up-Regulation (genetics, immunology)
• Viral Matrix Proteins (genetics, immunology)