1992 Fiscal Year Final Research Report Summary
The transcriptional factor involved in the constitutive expression of interleukin-6 in multiple myeloma
| Project/Area Number |
03671189
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TANABE Osamu Hiroshima Univ. School of Medicine, Research associate, 医学部, 助手 (70221398)
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| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Atsushi Hiroshima University Research Institute for Nuclear Medicine and Biology, Profes, 原爆放射能医学研究所, 教授 (50034070)
KAWANO Michio Hiroshima University Hospital, Assistant Professor, 医学部附属病院, 講師 (40161343)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Multiple Myeloma / Interleukin-6 / Autocrine / Growth Factor / Transcriptional Factor / NF-IL6 |
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| Research Abstract |
The purpose of this research project is to understand the pathogenesis of multiple myeloma by clarifying the mechanism of constitutive production of its autocrine growth factor, interleukin-6 (IL-6). It has been shown that, in human glioblastoma cell line SK-MG-4, IL-1 induced transcriptional activation of the IL-6 gene is mediated by a transcriptional factor NF-ILF6, which binds to a specific DNA sequence in the promoter region of the IL-6 gene. In order to test the possibility that NF-IL6 might be involved also in the constitutive expression of IL-6 in myeloma cells, we analyzed expression of both IL-6 and NF-IL6 mRNA in myeloma cells using the RT-PCR method. In all of the tested myeloma cells, including human myeloma cell lines, KMS-5 and U266 as well as primarily cultured myeloma cells, we could detect expression of both IL-6 and NF-IL6 mRNA, whose intensities were comparable to or even stronger than those of the human peripheral mononuclear cells stimulated with PHA and TPA. Moreover, we could detect NF-IL6 activity as a sequence specific DNA binding protein in nuclear extracts of those myeloma cells by gel shift assay probed with a synthetic oligonucleotide corresponding to a NF-IL6 binding sequence. In normal tissues, NF-IL6 mRNA is not expressed ordinarily, but expressed transiently upon stimulation with LPS or several cytokines, including IL-1. Our data showing the constitutive expression of NF-IL6 mRNA and activity in myeloma cells without any stimulation suggest the possibility that the constitutive expression of NF-IL6 may be responsible for the constitutive and deregulated production of IL-6 in myeloma cells.
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