Differential induction of the mitogen-activated protein kinase pathway by bacterial lipopolysaccharide in cultured monocytes and astrocytes Available to Purchase

We recently reported that cyclic AMP (cAMP) specifically inhibits lipopolysaccharide (LPS)-induced interleukin 1β (IL-1β) transcription initiation in astrocytic cells but enhances the LPS induction of IL-1β in monocytic cells. The purpose of this study was to determine how cAMP differentially regulates LPS-induced IL-1β transcription in these two cell types. Two essential components of the mitogen-activated 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 may be linked to the regulation of IL-1β transcription. In the human astrocytic cell line, U-373MG, LPS was found to strongly activate (and cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell line, THP-1, LPS minimally activated ERK2 and did not activate Raf-1. These findings suggest that, in astrocytic cells, elevated intracellular cAMP levels may negatively regulate LPS activation of IL-1β via the MAP kinase signalling pathway. In contrast, this pathway is not significantly activated by LPS in monocytic cells, thus inhibition by elevated intracellular cAMP levels would not affect IL-1β transcription.