Differential transcriptional regulation of silencer of death domains in cord blood and peripheral blood lymphocytes.
We have shown that neonatal lymphocytes are deficient in TNF-induced apoptosis. Recently, a 60 kDa protein termed silencer of death domains (SODD) has been shown to prevent spontaneous apoptosis. The binding of SODD to DD of the TNFR-I maintains DD in monomeric form and prevents their aggregation which is required for the apoptotic signal. We examined the expression of SODD mRNA during TNF-induced apoptosis. Although in non-stimulated cord blood lymphocytes the constitutive expression of SODD mRNA was lower than that of non-stimulated peripheral blood lymphocytes, following anti-CD3 stimulation SODD mRNA was significantly increased in cord blood lymphocytes at 12 and 24 h, returning to the baseline at 48 h. In contrast, a modest decrease in SODD transcript was observed in peripheral blood lymphocytes. Furthermore, TNF downregulated SODD mRNA expression in peripheral blood lymphocytes, whereas it had no significant effect on SODD transcripts in cord blood lymphocytes. Therefore, differential regulation of SODD may be one of the mechanisms responsible for decreased TNF-induced apoptosis in neonatal lymphocytes.
Laboratories of Molecular Biology and Cellular Immunology, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
J
J
Park
C
C
Kim
S
S
Gupta
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; C116906:BAG4 protein, human; D017252:CD3 Complex; D002352:Carrier Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha