STAT6 and the regulation of CD23 expression in B-chronic lymphocytic leukemia.
High CD23 expression is a hallmark of B-CLL cells. It is lost during in vitro culture and can be reinduced by IL-4, albeit to a lower extent than in normal B cells. To elucidate the events controlling CD23 expression in B-CLL cells, the IL-4 mediated induction of STAT6 was investigated. Western-blot analysis demonstrated that B-CLL cells contain comparable amounts of STAT6. Electrophoretic mobility shift assays (EMSA) showed no constitutive nuclear translocation of STAT6. IL-4 induced the translocation of STAT6 in B-CLL cells from all 22 patients investigated. The increase was transient, dose and time dependent without a distinct difference between B-CLL cells and non-malignant B cells. However, in contrast to normal B lymphocytes no strict correlation between CD23 expression and STAT6 activation was detected in B-CLL. Therefore further signalling pathways and transcription factors in addition to STAT6 have to be activated to explain the high expression of CD23 in B-CLL cells. For example, STAT1 which is induced by IFN-gamma and binds to the classical STAT6 site. It might be involved in the strong induction of CD23 on B-CLL cells after cotreatment with IL-4 and IFN-gamma, while in non-malignant B lymphocytes IFN-gamma leads to a reduction of IL-4 mediated CD23 expression.
Kneitz
C
C
Medizinische Poliklinik, University of Würzburg, Klinikstr. 6-8, D-97070, Würzburg, Germany. christian.kneitz@mail.uni-wuerzburg.de
Goller
M
M
Seggewiss
R
R
Yaman
A
A
Serfling
E
E
Tony
H P
HP
D001692:Biological Transport; D023201:CD40 Ligand; D004268:DNA-Binding Proteins / Q000032:analysis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D017455:Receptors, IgE / Q000032:analysis*; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000032:analysis* / Q000378:metabolism
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D023201:CD40 Ligand; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate