Elevated expression of proto-oncogenes during interleukin-5-induced growth and differentiation of murine B lineage cells.
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 30 min of stimulation with IL-5 and reached a maximal level by 1 hr. 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.
Migita
M
M
Department of Biology, Kumamoto University Medical School.
Yamaguchi
N
N
Katoh
S
S
Mita
S
S
Matsumoto
R
R
Sonoda
E
E
Tsuchiya
H
H
Matsuda
I
I
Tominaga
A
A
Takatsu
K
K
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D007075:Immunoglobulin M / Q000276:immunology; D015848:Interleukin-5 / Q000494:pharmacology*; D007700:Kinetics; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007075:Immunoglobulin M; D015848:Interleukin-5; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate