Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells.
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.
Hurme
M
M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Serkkola
E
E
Ronni
T
T
Silvennoinen
O
O
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007546:Isoquinolines / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D005576:Colforsin; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate