Inhibition of microglial cell RANTES production by IL-10 and TGF-β

Shuxian Hu, Chun C. Chao, Laura C. Ehrlich, Wen S. Sheng, Richard L. Sutton, Gaylan L. Rockswold, Phillip K. Peterson

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)815-821
Number of pages7
JournalJournal of Leukocyte Biology
Volume65
Issue number6
DOIs
StatePublished - 1999

Keywords

  • Central nervous system
  • Cytokine
  • Inflammation
  • NF-κB

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    Hu, S., Chao, C. C., Ehrlich, L. C., Sheng, W. S., Sutton, R. L., Rockswold, G. L., & Peterson, P. K. (1999). Inhibition of microglial cell RANTES production by IL-10 and TGF-β. Journal of Leukocyte Biology, 65(6), 815-821. https://doi.org/10.1002/jlb.65.6.815