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. 1993 May;92(2):347–352. doi: 10.1111/j.1365-2249.1993.tb03403.x

Inhibition by glucocorticoid and staurosporine of IL-4-dependent CD23 production in B lymphocytes is reversed on engaging CD40.

A Katira 1, K A Knox 1, M Finney 1, R H Michell 1, M Wakelam 1, J Gordon 1
PMCID: PMC1554800  PMID: 7683590

Abstract

IL-4 synergizes with signals delivered through CD40 both for the induction of CD23/Fc epsilon RII expression and for IgE synthesis. Moreover, engagement of CD40 on the B cell surface by MoAb overcomes the ability of interferons, transforming growth factor-beta, or anti-CD19 to inhibit IL-4-dependent change. We now report that occupancy of CD40 relieves potent suppression of IL-4-induced CD23 production by glucocorticoid or the relatively broad-acting kinase inhibitor staurosporine. Interruption of the IL-4 signal was observed with concentrations of staurosporine considered to be selective for protein kinase C (PKC) inhibition (IC50 = 10 nM) but not with genistein or tyrphostins, effective inhibitors of tyrosine kinase activity. On ligation of CD40, staurosporine no longer inhibited the IL-4 signal: at concentrations of between 1 and 20 nM, staurosporine actually increased by as much as 100% the rate of CD23 production stimulated on simultaneous activation through CD40 and IL-4R. Such augmentation was not observed when the more specific PKC inhibitor RO-31-8220 was used; indeed, CD40 engagement was unable to overcome the ability of this inhibitor to block IL-4-promoted CD23 induction (IC50 = 10 microM). Occupancy of CD40 did, however, thwart completely the usual ability of prednisolone to inhibit the IL-4 signal leading to CD23 induction. Activation through CD40 left inhibition of phorbol ester-induced CD23 expression by staurosporine, RO-31-8220, or glucocorticoid unchecked. These findings further highlight the intimate level of cross-talk existing between CD40 and IL-4R on resting B lymphocytes to promote CD23 expression, a phenotypic change which preludes IgE synthesis.

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Selected References

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