| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Atsushi Research Institute for Nuclear Medicine and Biology, Hiroshima Univ., Professor, 原爆放射能医学研究所, 教授 (50034070)
FUJIMURA King Research Institute for Nuclear Medicine and Biology, Hiroshima Univ., Associate, 原爆放射能医学研究所, 助教授 (80034114)
TANABE Osamu Medical Hospital, Hiroshima Unv., Research Associate, 医学部・附属病院, 助手 (70221398)
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| Research Abstract |
Human myeloma cells constitutively produce interleukin-6 (IL-6) and express IL-6 receptor, and an autocrine loop by IL-6 is operating in myeloma cells. Constitutive expression of IL-6 gene is considered to be closely associated with oncogenesis of myeloma. In order to confirm this, we investigated whether plasma cells in a pre-myeloma state, benign monoclonal gammopathy, produced IL-6 significantly. These plasma cells did not express any significant IL-6mRNA. This is suggestive that constitutive expression of IL-6 gene is characteristic of myeloma cells. We also established human myeloma cell lines and selected one myeloma cell line, KMS-5, which showed higher expression of IL-6mRNA. As for soluble factors modulating IL-6 gene expression, interleukin-1 (IL-1) was found to increase IL-6mRNA in myeloma cells, and interferon alpha and glucocorticoids decreased IL-6mRNA. We focused on the IL-1-induced IL-6 gene activation in myeloma cells. Transcriptional enhancer sequence concerning in IL-1-induced IL-6 gene activation has been identified as the palindrome sequence, ACATTGCACAATCT. NF-IL6 was identified to specifically bind to the IL-1-responsive element, and the gene encoding NF-IL6 has been cloned. We investigated the relationship between IL-6 and NF-IL6 expression in myeloma cells by RT-PCR and Northern blotting, and NF-IL6 expression were detected in all myeloma cells. On the other hand, there were not any structural alterations of IL-6 gene in myeloma cells by Southern blotting. Taken together, we consider that constitutive expression of IL-6 gene in human myeloma cells may be due to the altered expression of its transcriptional factor, NF-IL6. Further investigation on the mechanism of IL-6 gene activation is now in progress ; 1) the effect of induction of anti-sense NF-IL6 on IL-6 gene expression, and 2) identification of other transcriptional factors.
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