Inhibitors of protein tyrosine kinases and protein tyrosine phosphatases suppress IL-4-induced CD23 expression and release by human B lymphocytes.
The pleiotropic lymphokine IL-4 is a growth and differentiation factor for human B cells. IL-4 induces the expression of the CD23 (Fc epsilon RII) molecule on B lymphocytes and promotes the release of its soluble form (sCD23); the cleavage fragments of the latter have been reported to modulate IL-4-dependent IgE biosynthesis. In the present work, we have tested the effects of inhibitors of protein tyrosine kinases (PTK) and protein phosphatases (PP) on the induction by IL-4 of the membrane and soluble forms of CD23. The PTK inhibitors genistein and lavendustin A were found to suppress, in a dose-dependent way, the induction by IL-4 of CD23 membrane expression as well as CD23 release by resting and SAC-preactivated B lymphocytes. No such suppression was detected with inhibitors of serine and threonine kinases. The addition of the protein tyrosine phosphatase (PTP) inhibitor sodium orthovanadate also resulted in a marked decrease in CD23 induction by IL-4. Cell viability was little affected by these inhibitors. However, a diminution of the large activated B cell population was observed, which correlated with an inhibition of the entry in the S phase. Partial inhibition of sCD23 release was also observed with okadaic acid and calyculin A, two inhibitors of serine/threonine PP, but only at concentrations which block PP1 in addition to PP2A. These results suggest that protein tyrosine phosphorylation and dephosphorylation may play a major role in IL-4 signalling. This conclusion was strengthened by the observation that a mAb anti-CD45, a membrane tyrosine phosphatase, inhibited IL-4-induced sCD23 release by B lymphocytes.
Kolb
J P
JP
U365 INSERM, Interférons et Cytokines, Institut Curie, Paris, France.
Abadie
A
A
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019833:Genistein; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D007529:Isoflavones / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017455:Receptors, IgE / Q000096:biosynthesis*; D014638:Vanadates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007529:Isoflavones; D010636:Phenols; D017455:Receptors, IgE; D015847:Interleukin-4; D014638:Vanadates; C062898:lavendustin A; D019833:Genistein; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases