INTERFERON-GAMMA ENHANCES THE LPS-INDUCED G-CSF GENE-EXPRESSION IN HUMAN ADHERENT MONOCYTES, WHICH IS REGULATED AT TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS

Human adherent monocytes were studied with regard to the expression of granulocyte colony-stimulating factor (G-CSF) at mRNA and protein lev els in response to lipopolysaccharide (LPS) and gamma-interferon (IFN- gamma) stimulation. Monocytes did not express G-CSF transcripts in res ponse to IFN-gamma treatment. In contrast, monocytes exposed to IFN-ga mma plus LPS showed a dose-dependent increase in G-CSF mRNA accumulati on and protein secretion compared to LPS-stimulated monocytes. The aug mented G-CSF mRNA expression in response to IFN-gamma plus LPS was the result of a slight increase in the G-CSF transcription rate (2.2-fold ) and a more than 6-fold increase in the G-CSF mRNA half-life (20 minu tes vs. > 120 minutes). In addition, it was shown that the effects of IFN-gamma on LPS-induced G-CSF protein secretion could be mimicked by the calcium ionophore A23187, suggesting that the Ca2+-dependent pathw ay might be triggered after binding of the ligand to the receptor. Fin ally, it was observed that the potentiating effects of IFN-gamma on LP S-induced G-CSE: secretion could be blocked by interleukin-4 (IL4). Th ese data indicate that two cytokines produced by activated T cells hav e opposite effects on G-CSF production by human activated monocytes.