Modulation of glial activation by astrocyte-derived protein S100B: differential responses of astrocyte and microglial cultures

The astrocyte-derived protein S100B stimulates production of inducible nitr ic oxide synthase and nitric oxide (NO) in astrocytes [Hu et al., 1996, J. Biol. Chem. 271:2543], but its effect on microglia is not known. In additio n, S100B's ability to modulate the activity of other glial activating agent s has not been defined. In this study, we compared the ability of S100B to stimulate NO in cultures of rat primary astrocytes and the BV-2 murine micr oglial cell line, and investigated the effect of the combined action of S10 0B and other stimuli known to activate glial cells. S100B itself stimulated the production of NO in astrocytes, and did not modify or potentiated only weakly the NO production induced by interleukin-l beta, tumor necrosis fac tor alpha, dibutyryl cyclic AMP, zymosan A or lipid A. In contrast, S100B a lone did not induce NO in BV-2 cells but strongly potentiated NO production in the presence of lipid A but not zymosan A. The deletion of eight C-term inal amino acid residues in S100B leads to a loss of the effect of S100B on microglia but not on astrocytes. These results demonstrate that responses of glial cells to extracellular S100B can vary depending on the cell type, and suggest that different structural features of S100B are important for t he protein's effects on microgolia and astrocytes. (C) 2000 Elsevier Scienc e B.V. All rights reserved.