TY - JOUR
T1 - Inhibition of microglial cell RANTES production by IL-10 and TGF-β
AU - Hu, Shuxian
AU - Chao, Chun C.
AU - Ehrlich, Laura C.
AU - Sheng, Wen S.
AU - Sutton, Richard L.
AU - Rockswold, Gaylan L.
AU - Peterson, Phillip K.
PY - 1999
Y1 - 1999
N2 - Using human fetal microglial cell cultures, we found that the gram- negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)-κB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α dose-dependently stimulated microglial cell RANTES production via NF-κB activation. Anti-inflammatory cytokines, IL-10, and transforming growth factor (TGF)-β sequentially inhibited LPS- and cytokine- induced microglial cell NF-κB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti-inflammatory cytokines IL-10 and TGF-β down-regulate the production of this β-chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain.
AB - Using human fetal microglial cell cultures, we found that the gram- negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)-κB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α dose-dependently stimulated microglial cell RANTES production via NF-κB activation. Anti-inflammatory cytokines, IL-10, and transforming growth factor (TGF)-β sequentially inhibited LPS- and cytokine- induced microglial cell NF-κB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti-inflammatory cytokines IL-10 and TGF-β down-regulate the production of this β-chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain.
KW - Central nervous system
KW - Cytokine
KW - Inflammation
KW - NF-κB
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U2 - 10.1002/jlb.65.6.815
DO - 10.1002/jlb.65.6.815
M3 - Article
C2 - 10380904
AN - SCOPUS:0033039422
SN - 0741-5400
VL - 65
SP - 815
EP - 821
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -