Upregulation of CD38 gene expression in leukemic B cells by interferon types I and II.
The activation antigen CD38, which has NAD+ glycohydrolase activity in its extracellular domain, is expressed by a large variety of cell types. Few investigations into the regulation of CD38 expression by physiologic stimuli have been reported. As the CD38 promoter contains potential binding sites for interferon (IFN) regulatory factor-1 (IRF-1), we investigated the influence of IFN type I (alpha and beta) and type II (gamma) on CD38 gene expression of leukemic B cells. Using the IFN-responsive B cell line Eskol, we found by RT-PCR analysis a rapid time-dependent induction in CD38 mRNA (starting at 6 h) with each type of IFN. This induction was independent of protein synthesis, suggesting that CD38 gene activation does not require IRF-1 but is merely under direct transcriptional regulation by latent IFN-inducible factors. mRNA stimulation was followed within 24 h by induction of membrane CD38, which coincided with rises of CD38-specific ectoenzymatic activities, that is, NAD+ glycohydrolase, (A/G)DP-ribosyl cyclase, and cyclic ADP ribose hydrolase activities. IFN failed to induce or upregulate the other CD38-related ectoenzymes analyzed, that is, CD39, CD73, CD157, and PC-1. Similarly, treatment of leukemic cells of patients with B chronic lymphocytic leukemia (B-CLL) with IFN resulted in an increase in CD38 mRNA mirrored by plasma membrane upregulation of CD38 and NAD+ glycohydrolase activity. Further investigation in relation to CD38 gene activation and B-CLL behavior remains to be defined.
Bauvois
B
B
Unité 365 INSERM, Institut Curie, Paris, France. bbauvois@curie.fr
Durant
L
L
Laboureau
J
J
Barthélémy
E
E
Rouillard
D
D
Boulla
G
G
Deterre
P
P
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1