Regulation of interleukin-10 gene expression: possible mechanisms
accounting for its upregulation and for maturational differences in its
expression by blood mononuclear cells
T Le, L Leung, WL Carroll and KR Schibler
Department of Pediatrics, Clinical Research Center, University of Utah
School of Medicine, Salt Lake City 84132, USA.
Interleukin-10 (IL-10) downmodulates phagocytic immune responses and
accentuates humoral responses. Human neonates exhibit broad immune deficits
that parallel actions of IL-10. We postulated that IL-10 production would
be diminished in neonatal blood cells. We found that IL-10 production by
lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMNCs)
in vitro was greater by adult cells than by term cells and preterm cells.
Additional studies were undertaken to identify mechanisms responsible for
the developmental differences in IL- 10 gene expression. IL-10
transcription was present in freshly isolated adult and neonatal cells in
the absence of detectable levels of transcript. Transcription rates were
not different between adult and neonatal cells. IL-10 transcripts were
approximately 40% more abundant in adult cells than in term cells and were
consistent with differences in secreted protein; however, no differences
were noted in mRNA stability. IL-10 half-life was 60 minutes for both adult
and term PBMNCs. We conclude that up-regulation of IL-10 gene expression in
PBMNCs is modulated at the post-transcriptional level, that IL-10 protein
production and mRNA content are greater in activated cells from adults
compared with those from neonates, and that maturational differences in
IL-10 expression are not due to differences in transcription rate or mRNA
stability. Maturational differences in IL-10 expression might be due to
differences in subpopulations of cytokine- producing cells or differences
in nucleo-cytoplasmic transport.
Volume 89,
Issue 11,
pp. 4112-4119,
06/01/1997
Copyright © 1997 by The American Society of Hematology
