The 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
2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 117, no 1, 165-174 p.Article in journal (Refereed) Published
In line with the B-lymphotropic nature of 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 EBNA-1 and LMPs (type II latency) in the classical Hodgkin lymphomas (cHL). We have previously reported that exposure of the in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and 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. The induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer 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, co-culture of EBV-carrying BL cells with activated CD4(+) T cells resulted in the induction of LMP-1 in the absence of EBNA-2. As the Hodgkin/Reed-Sternberg 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 the EBV-positive cHLs.
Place, publisher, year, edition, pages
2011. Vol. 117, no 1, 165-174 p.
Research subject Immunology
IdentifiersURN: urn:nbn:se:su:diva-44312DOI: 10.1182/blood-2010-01-265272ISI: 000285963900026PubMedID: 20876453OAI: oai:DiVA.org:su-44312DiVA: diva2:360952
authorCount :82010-11-052010-11-052013-08-29Bibliographically approved