DIFFERENT ACTIVATION SIGNALS ARE REQUIRED FOR THE EXPRESSION OF INTERLEUKIN-1 ALPHA-GENES AND BETA-GENES IN HUMAN MONOCYTES

The production and MRNA expression of IL-1-alpha and IL-1-beta by human monocytes was examined after two different stimuli, a protein kinase C (PKC) activator phorbol myristate acetate (PMA) and bacterial lipopolysaccharide (LPS). LPS induced production of high levels of both IL-1-alpha and IL-1-beta protein (quantitated with type-specific ELISA assays), while after PMA stimulation only IL-1-beta protein could be detected. The IL-1-alpha and IL-1-beta mRNA levels quantitated by Northern blotting were in line with the respective protein levels and nuclear run off analysis revealed that PMA did not activate the IL-1-alpha transcription. The production of the IL-1-alpha and IL-1-beta protein as well as the mRNA expression could be inhibited with protein kinase inhibitor H7, but not with HA 1004, indicating that PKC activation is essential for the activation of these genes. Thus these data indicate that PKC activation alone is sufficient for the induction of the IL-1-beta gene, but some additional signals (provided by LPS) are required for the activation of the IL-1-alpha gene.