Inhibition of serotonin-induced Ca 2+ mobilization by interleukin-1β in rat C6BU-1 glioma cells

Abstract

To study the potential interaction between cytokine and serotonin (5-HT) signal transduction, we evaluated the effect of interleukin-1β (IL-1β) on the 5-HT 2 receptor-mediated mobilization of intracellular Ca 2+ in cultured rat C6BU-1 glioma cells. Pretreatment of cells with IL-1β significantly inhibited the 5-HT-induced mobilization of Ca 2+ in a dose (30–1000 U/ml)- and time (12–24 h)-dependent manner. Inhibition was observed when cells were stimulated with concentrations of 5-HT of ≥ 1 μM, which induced the maximal 5-HT response. Lipopolysaccharide (1 μg/ml) also inhibited 5-HT-induced Ca 2+ mobilization, but heat-inactivated IL-1β as well as interferon-α (1000 U/ml), interferon-γ (1000 U/ml), and tumor necrosis factor-α (2000 U/ml) did not. The inhibitory effects of IL-1β and LPS were significantly prevented by genistein, a selective tyrosine kinase antagonist, and by H7, a potent inhibitor of protein kinase C. These results indicate that IL-1β and LPS inhibit 5-HT 2 receptor-mediated Ca 2+ mobilization via pathways that include the activation of a tyrosine kinase and protein kinase C. The interaction between cytokines (IL-1β) and monoamines (5-HT) may serve to modulate signal transduction in the central nervous system.