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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
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- Kis, Loránd L. (author)
- Karolinska Institutet
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- Gerasimcik, Natalija, 1980- (author)
- Stockholms universitet,Avdelningen för cellbiologi,Vilnius University
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- Salamon, Daniel (author)
- Karolinska Institutet
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- Klein, Eva (author)
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- (creator_code:org_t)
- American Society of Hematology, 2011
- 2011
- English.
- In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:1, s. 165-174
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- immunologi
- Immunology
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- art (subject category)
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- Kis, Loránd L.
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- Salamon, Daniel
- Persson, Emma K.
- Nagy, Noémi
- Klein, George
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- Severinson, Eva
- Klein, Eva
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- About the subject
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- NATURAL SCIENCES
- NATURAL SCIENCES
- and Biological Scien ...
- and Immunology
- Articles in the publication
- Blood
- By the university
- Stockholm University
- Karolinska Institutet
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