DIFFERENTIAL INDUCTION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY BY BACTERIAL LIPOPOLYSACCHARIDE IN CULTURED MONOCYTES AND ASTROCYTES

We recently reported that cyclic AMP (cAMP) specifically inhibits lipo polysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcript ion initiation in astrocytic cells but enhances the LPS induction of I L-1 beta in monocytic cells, The purpose of this study was to determin e how cAMP differentially regulates LPS-induced IL-1 beta transcriptio n in these two cell types. Two essential components of the mitogen-act ivated protein (MAP) kinase signal-transduction pathway, extracellular -signal-regulated kinase (ERK2; p41(mapk)) and Raf-1, have been shown to be targets of LPS stimulation in other cell types, and therefore ma y be linked to the regulation of IL-1 beta transcription. In the human astrocytic cell line, U-373MG, LPS was found to strongly activate (an d cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell li ne, THP-1, LPS minimally activated ERK2 and did not activate Raf-1. Th ese findings suggest that, in astrocytic cells, elevated intracellular cAMP levels may negatively regulate LPS activation of IL-1 beta via t he MAP kinase signalling pathway. In contrast, this pathway is not sig nificantly activated by LPS in monocytic cells, thus inhibition by ele vated intracellular cAMP levels would not affect IL-1 beta transcripti on.