Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg tumor cell line by a novel IL-13 antagonist.

Abstract

IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed-Sternberg tumor cells (H/RS cells). Since we have recently identified and produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological activity of IL-13, here we examined whether IL-13E13K can inhibit growth of Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed IL-13 message and protein and message for various chains of IL-13R. H/RS cell lines expressed mRNA for the IL-13R alpha 1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha 2 chain. An H/RS cell line (L1236) internalized the ligand-receptor complex after binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin A (IL-13-PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was specifically cytotoxic to H/RS cells in vitro. These results indicate that IL-13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 H/RS cell line. Therefore, additional studies should be performed to determine the expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma and both agents should be further tested in vitro and in vivo as possible therapeutic agents for HL.

• Authors: Y Oshima, R K Puri
• Journal: Cellular immunology (Cell Immunol) Vol. 211 Issue 1 Pg. 37-42 (Jul 10 2001) ISSN: 0008-8749 [Print] Netherlands
• PMID: 11585386 (Publication Type: Journal Article)

Chemical References

• IL13RA1 protein, human
• Interleukin-13
• Interleukin-13 Receptor alpha1 Subunit
• RNA, Messenger
• Receptors, Interleukin
• Receptors, Interleukin-13
• interleukin 13 antagonist E13K

Topics

• Autocrine Communication
• Cell Division
• Endocytosis
• Hodgkin Disease (drug therapy, metabolism, pathology)
• Humans
• Interleukin-13 (antagonists & inhibitors, biosynthesis, genetics, pharmacology)
• Interleukin-13 Receptor alpha1 Subunit
• RNA, Messenger (biosynthesis)
• Receptors, Interleukin (biosynthesis, genetics, physiology)
• Receptors, Interleukin-13
• Reed-Sternberg Cells (drug effects, metabolism, pathology)
• Tumor Cells, Cultured