Elevated Expression of Proto-Oncogenes during Interleukin-5-Induced Growth and Differentiation of Murine B Lineage Cells

  • MIGITA Masahiro
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • YAMAGUCHI Naoto
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • KATOH Shigeki
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • MITA Seiji
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • MATSUMOTO Ryoji
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • SONODA Eiichiro
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • TSUCHIYA Hiroyuki
    Department of Pediatrics, Kumamoto University Medical School
  • MATSUDA Ichiro
    Department of Pediatrics, Kumamoto University Medical School
  • TOMINAGA Akira
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School
  • TAKATSU Kiyoshi
    Department of Biology, Institute for Medical Immunology, Kumamoto University Medical School

抄録

Interleukin 5 (IL-5), a lymphokine produced by helper T cells, is involved in the regulation of growth and differentiation of B cells and other hematopoietic cells. To elucidate IL-5-mediated intracellular mechanisms, we have established IL-5-dependent and -independent murine early B cell lines, J6 and MJ88-1, respectively, and examined the effect of IL-5 on the expression of proto-oncogenes during proliferation. Two- to 3.5-fold increases in the levels of c-myb, c-myc, c-fos, and c-fms mRNA were observed in J6 cells, compared with those in MJ88-1 cells. Further, a role of IL-5 in the proto-oncogene expression during differentiation was examined by using thymidine-treated murine B-cell chronic leukemia BCL1-B20 cells with growth arrest. After 4-day culture, the amount of IgM secreted from BCL1-B20 cells was augmented 4-6 fold in the presence of IL-5. Although expression of c-myb, c-fos, and c-fms mRNA did not change, only c-myc mRNA expression was elevated within 30min of stimulation with IL-5 and reached a maximal level by 1hr. Addition of phorbol 12-myristate 13-acetate (PMA) or IL-4 to the culture of BCL1-B20 cells inhibited both the IL-5-mediated augmentation of IgM secretion and the elevated expression of c-myc mRNA. These findings suggest that the IL-5 signal may be associated with the up-regulation of c-myc expression.

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