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STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma.
Blood. 2011 Jan 06; 117(1):165-74.Blood

Abstract

In line with the B-lymphotropic nature of Epstein-Barr virus (EBV), the virus is present in several types of B-cell lymphomas. EBV expresses a different set of latent genes in the associated tumors, such as EBV nuclear antigen 1 (EBNA-1) and latent membrane proteins (LMPs; type II latency) in classical Hodgkin lymphomas (HLs). We previously reported that exposure of in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and interleukin-4 (IL-4) induced the expression of LMP-1. Here, we show that exposure to IL-4 or IL-13 alone induced LMP-1 in the absence of EBNA-2. Induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer signal transducer and activator of transcription 6 (STAT6) and a newly defined high-affinity STAT6-binding site in the LMP-1 promoter. IL-4 induced LMP-1 also in Burkitt lymphoma-derived lines and in tonsillar B cells infected with the EBNA-2-deficient EBV strain P3HR-1. Furthermore, coculture of EBV-carrying Burkitt lymphoma cells with activated CD4(+) T cells resulted in the induction of LMP-1 in the absence of EBNA-2. Because Hodgkin/Reed-Sternberg cells are known to secrete IL-13, to have constitutively activated STAT6, and to be closely surrounded by CD4(+) T cells, these mechanisms may be involved in the expression of LMP-1 in EBV-positive chronic HLs.

Authors+Show Affiliations

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. lorand.kis@karolinska.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20876453

Citation

Kis, Loránd L., et al. "STAT6 Signaling Pathway Activated By the Cytokines IL-4 and IL-13 Induces Expression of the Epstein-Barr Virus-encoded Protein LMP-1 in Absence of EBNA-2: Implications for the Type II EBV Latent Gene Expression in Hodgkin Lymphoma." Blood, vol. 117, no. 1, 2011, pp. 165-74.
Kis LL, Gerasimcik N, Salamon D, et al. STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma. Blood. 2011;117(1):165-74.
Kis, L. L., Gerasimcik, N., Salamon, D., Persson, E. K., Nagy, N., Klein, G., Severinson, E., & Klein, E. (2011). STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma. Blood, 117(1), 165-74. https://doi.org/10.1182/blood-2010-01-265272
Kis LL, et al. STAT6 Signaling Pathway Activated By the Cytokines IL-4 and IL-13 Induces Expression of the Epstein-Barr Virus-encoded Protein LMP-1 in Absence of EBNA-2: Implications for the Type II EBV Latent Gene Expression in Hodgkin Lymphoma. Blood. 2011 Jan 6;117(1):165-74. PubMed PMID: 20876453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma. AU - Kis,Loránd L, AU - Gerasimcik,Natalija, AU - Salamon,Daniel, AU - Persson,Emma K, AU - Nagy,Noémi, AU - Klein,George, AU - Severinson,Eva, AU - Klein,Eva, Y1 - 2010/09/27/ PY - 2010/9/30/entrez PY - 2010/9/30/pubmed PY - 2011/2/25/medline SP - 165 EP - 74 JF - Blood JO - Blood VL - 117 IS - 1 N2 - In line with the B-lymphotropic nature of Epstein-Barr virus (EBV), the virus is present in several types of B-cell lymphomas. EBV expresses a different set of latent genes in the associated tumors, such as EBV nuclear antigen 1 (EBNA-1) and latent membrane proteins (LMPs; type II latency) in classical Hodgkin lymphomas (HLs). We previously reported that exposure of in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and interleukin-4 (IL-4) induced the expression of LMP-1. Here, we show that exposure to IL-4 or IL-13 alone induced LMP-1 in the absence of EBNA-2. Induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer signal transducer and activator of transcription 6 (STAT6) and a newly defined high-affinity STAT6-binding site in the LMP-1 promoter. IL-4 induced LMP-1 also in Burkitt lymphoma-derived lines and in tonsillar B cells infected with the EBNA-2-deficient EBV strain P3HR-1. Furthermore, coculture of EBV-carrying Burkitt lymphoma cells with activated CD4(+) T cells resulted in the induction of LMP-1 in the absence of EBNA-2. Because Hodgkin/Reed-Sternberg cells are known to secrete IL-13, to have constitutively activated STAT6, and to be closely surrounded by CD4(+) T cells, these mechanisms may be involved in the expression of LMP-1 in EBV-positive chronic HLs. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/20876453/STAT6_signaling_pathway_activated_by_the_cytokines_IL_4_and_IL_13_induces_expression_of_the_Epstein_Barr_virus_encoded_protein_LMP_1_in_absence_of_EBNA_2:_implications_for_the_type_II_EBV_latent_gene_expression_in_Hodgkin_lymphoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)60152-5 DB - PRIME DP - Unbound Medicine ER -