Induction of S100A4, S100A6, and galectin-1 during the lineage commitment of CD4+CD8+ thymocyte cell line is suppressed by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
To study the mechanisms underlying the linage commitment of CD4+CD8+ thymocytes and the skewed differentiation of CD4+CD8+ into CD4-CD8+ thymocytes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we stimulated with antigen DPK cells, a CD4+CD8+ thymic lymphoma cell line which can differentiate into CD4+CD8- thymocytes and performed a comparative proteomic analysis of DPK cells stimulated with antigen or not. Among the 10 up-regulated or induced proteins upon antigenic stimulation, S100A4, S100A6, and galectin-1 were highly up-regulated. Kinetic studies revealed that expression of S100A4, S100A6, and galectin-1 was dramatically increased as early as 10min after antigen stimulation, similar to that of cKrox and Runx3, transcription factors intimately associated with the lineage commitment. Among four thymocyte subpopulations of the thymus examined, S100A4, S1006, and galectin-1 were most prominently expressed in CD4+CD8+ thymocytes, but not at all in CD4-CD8+ and CD4-CD8- thymocytes. In the spleen, expression of S100A4, S1006, and galectin-1 was greater in CD4 than in CD8 splenocytes. When TCDD was added to antigen-stimulated DPK cells, antigen-induced up-regulation of S100A4, S1006, and galectin-1 were remarkably inhibited, probably partly accounting for the skewed differentiation of CD4+CD8+ into CD4-CD8+ thymocytes induced by TCDD.
Department of Biology, Changwon National University, #9 Sarim-dong, Changwon, Kyungnam 641-773, South Korea.
Chang-Hwan
CH
Jeon
Hye-Lin
HL
Kim
Joo-Hung
JH
Park
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004147:Dioxins / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D037483:Galectin 1 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D040901:Proteomics / Q000379:methods; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D018797:Cell Cycle Proteins; D004147:Dioxins; D037483:Galectin 1; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C489134:S100a6 protein, mouse; C038902:1,4-dioxin