A novel phenoxazine derivative suppresses surface IgM expression in DT40 B cell line.
1. 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one (Phx) has been demonstrated to be an actinomycin D-like phenoxazine, and to display anti-tumour activity. 2. In this study, we report on the effect of Phx on B cell antigen receptor (BCR) and receptor-mediated signalling in DT40 B cells. 3. Treatment of B cells with Phx for 12 h inhibited BCR-stimulated tyrosine phosphorylation of cellular proteins. 4. B cells exposed to Phx exhibited down-regulation of surface IgM which is part of BCR. In contracts with actinomycin D, Phx rapidly reduced the expression of IgM without decreasing the expression of other signalling molecules. 5. Analysis with confocal microscopy demonstrated that Phx treatment reduced IgM expression both at the cell surface and inside the cell. 6. Treatment of B cells with Phx resulted in the reduction of IgM secretion. Since MG-132, a proteasomal inhibitor, restored IgM contents to the control levels, Phx has the specific effect of accelerating IgM degradation. 7. These results suggest that Phx down-regulates the expression of IgM and inhibits BCR-mediated signalling and IgM secretion. Phx may be useful as an immunosuppressive agent for therapeutic purposes.
Gao
Sanyang
S
Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Takano
Tomoko
T
Sada
Kiyonao
K
He
Jinsong
J
Noda
Chiseko
C
Hori-Tamura
Naoko
N
Tomoda
Akio
A
Yamamura
Hirohei
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000187:drug effects*; D007976:Leupeptins / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
C104202:2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one; D015853:Cysteine Proteinase Inhibitors; D007075:Immunoglobulin M; D007976:Leupeptins; D010078:Oxazines; D011947:Receptors, Antigen, B-Cell; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde