Control of interleukin-1 beta expression by protein kinase C and cyclic
adenosine monophosphate in myeloid leukemia cells
M Hurme, E Serkkola, T Ronni and O Silvennoinen
Department of Bacteriology and Immunology, University of Helsinki, Finland.
We have examined the signal transduction pathways leading to the expression
of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells
lines. Two cell lines representing different stages of differentiation were
used (HL-60, promyelocytic, and THP-1, mature monocytic). In accordance
with previous studies, it was observed that a protein kinase C (PKC)
activator, phorbol myristate acetate (PMA), was a sufficient stimulus for
induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta
protein production in both of these cell lines. A structural analog of
cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous
cAMP levels (prostaglandin E2, forskolin) were not alone able to induce
IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta
production and IL-1 beta mRNA accumulation. Nuclear run off analysis showed
that this elevation in IL-1 beta mRNA levels was due to an increased rate
of transcription. If dbcAMP was added 6 hours before PMA to the cultures,
no enhancement in the IL-1 beta production was seen, implying that for this
enhancing effect both of these signals must be present simultaneously. PKC
inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1
beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no
effect, suggesting that PKA activation is not involved in the mechanism of
action of cAMP in this case. Collectively, the present findings show that
cAMP-dependent signals can have a positive regulatory effect on the
PKC-dependent activation of the IL-1 beta gene in cells derived from
different stages of myeloid differentiation.
Volume 76,
Issue 11,
pp. 2198-2203,
12/01/1990
Copyright © 1990 by The American Society of Hematology
