A functional role for interleukin (IL)-4-driven cyclic amp accumulation inhuman B lymphocytes

Interleukin-4 (IL-4) regulates the expression of the 55-kDa alpha-subunit ( CD25) of the IL-2 receptor complex in human B lymphocytes, This report sugg ests that the cAMP/protein kinase A (PKA) component of the IL-4 receptor si gnalling programme in human tonsillar B cells has a functionally important role in regulating expression of the CD25 gene by attenuating activity of a protein binding to a potent negative regulatory element (NRE) in the CD25 promoter; this effect can be mimicked by agents that elevate cAMP and block ed by inhibitors of PKA but not protein kinase C (PKC), In a B-cell line th at fails to elevate cAMP, attenuate NRE-binding protein (NRE-BP) activity o r express CD25 following IL-4 treatment, stimulation of cAMP accumulation b y forskolin facilitates IL-4-mediated induction of both the endogenous gene and an exogenous reporter gene under the control of a minimal promoter/enh ancer fragment of the CD25 gene. (C) 2000 Academic Press.