Interleukin-4 receptor regulation in human monocytic cells.
The regulation of the interleukin-4 receptor (IL-4R) was studied at mRNA and protein level in monocytic cells on stimulation with activators of different intracellular signaling pathways and IL-4. Activation of protein kinase C-dependent pathways with phorbol myristate acetate (PMA) or activation of protein kinase A-dependent pathways with DBcAMP and prostaglandin E2 resulted in an augmented IL-4R expression at mRNA and protein level. Transcriptional and posttranscriptional mechanisms seemed to be involved in the promotive effect of DBcAMP because the transcription rate increased 1.8-fold, and the half-life of IL-4R mRNA was prolonged to 150 minutes compared with 120 minutes in unstimulated cells. In contrast, the effect of PMA could only be ascribed to changes at transcriptional level. However, activation of Ca(2+)-dependent pathways with A23187 or stimulation with IL-4 had no effect on the IL-4R expression. The unresponsiveness to IL-4 could not be ascribed to a nonfunctional receptor because IL-4 did modulate the CD14, CD23, and HLA-DR antigen expression. These results are in contrast with IL-4R regulation in T cells, which is affected by IL-4- and Ca(2+)-dependent pathways. The discrepancy might be caused by the presence of the common IL-2 receptor gamma chain (gamma c) in T cells and the absence of the gamma c in monocytic cells, as has been shown by polymerase chain reaction. These data indicate that IL-4Rs are differentially regulated, depending on the cell type studied.
de Wit
H
H
Department of Internal Medicine, University of Groningen, The Netherlands.
Hendriks
D W
DW
Halie
M R
MR
Vellenga
E
E
D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis* / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4