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PMID: 10377189 Published · ppublish English Journal Article

Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells.

The Journal of experimental medicine ·Vol. 189 ·No. 12 ·1999-06-21 ·Pages 1939-46

Kapp U, Yeh WC, Patterson B, Elia AJ, Kägi D, Ho A, Hessel A, Tipsword M, Williams A, Mirtsos C, Itie A, Moyle M, Mak TW

Abstract

Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.

MeSH Terms
Cell Division/drug effects Gene Expression Regulation, Neoplastic Genes, Neoplasm Herpesvirus 4, Human/genetics Hodgkin Disease/genetics,immunology,pathology Humans Immunohistochemistry In Situ Hybridization Interleukin-13/genetics,metabolism,pharmacology Interleukin-15/metabolism Lymph Nodes/pathology Lymphoma, Non-Hodgkin/genetics RNA, Messenger/analysis Reed-Sternberg Cells/immunology,pathology Tumor Cells, Cultured
Chemicals
Interleukin-13 Interleukin-15 RNA, Messenger
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Kapp U
Amgen Institute, Ontario Cancer Institute, the Department of Medical Biophysics, and the Department of Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
Yeh W C
Patterson B
Elia A J
Kägi D
Ho A
Hessel A
Tipsword M
Williams A
Mirtsos C
Itie A
Moyle M
Mak T W
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.189.12.1939
Published
1999-06-21
Pages
1939-46
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192965
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.189.12.1939 PMC Full Text View journal details
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