A functional role for interleukin (IL)-4-driven cyclic amp accumulation in human 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 suggests that the cAMP/protein kinase A (PKA) component of the IL-4 receptor signalling 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 blocked by inhibitors of PKA but not protein kinase C (PKC). In a B-cell line that fails to elevate cAMP, attenuate NRE-binding protein (NRE-BP) activity or express CD25 following IL-4 treatment, stimulation of cAMP accumulation by forskolin facilitates IL-4-mediated induction of both the endogenous gene and an exogenous reporter gene under the control of a minimal promoter/enhancer fragment of the CD25 gene.
McKay
C E
CE
Division of Biochemistry & Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, G12 8QQ.
Hewitt
E L
EL
Ozanne
B W
BW
Cushley
W
W
D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D014066:Palatine Tonsil / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000502:physiology*; D015398:Signal Transduction; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D013449:Sulfonamides; D005576:Colforsin; D015847:Interleukin-4; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide