Inhibition of lipopolysaccharide-induced microglial activation by preexposure to neurotrophin-3

Shun Fen Tzeng, Hsin Ying Huang, Tsung I. Lee, Jeng Kuan Jwo

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Microglia activated by neural injuries produce pro-inflammatory mediators, but activated microglia also appear in developing neural tissue to phagocytose cell debris resulting from programmed cell death without inducing tissue damage. Thus, factors associated with the developing CNS may modulate microglial activities. Previously we reported that pretreatment with neurotrophin-3 (NT-3), a factor known to regulate neural development, inhibits the production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor-α, and interleukin-1β, in BV2 activated by inflammagen lipopolysaccaride (LPS). In this study, the inhibition of proinflammatory mediators by NT-3 pretreatment (preNT-3) in primary microglia with LPS stimulation was corroborated. Moreover, pretreatment of LPS-activated microglia with NT-3 induced a trend of reduction in phagocytotic ability. By using LPS-activated BV2 cells, we further found that reduced expression of inducible NO synthetase by preNT-3 was mediated by MAP kinase and PI3 kinase signaling pathways. Moreover, pretreatment of BV2 cells with NT-3 led to reduced levels of the p65 subunit of nucleus factor-κB (NFκB) and its DNA binding activity. Accordingly, our results indicate that preexposure of microglia to NT-3 leads to a reduced production of proinflammatory mediators in activated microglia by the induction of MAP kinase and PI3 kinase signaling, which in turn may reduce NFκB DNA binding activity. This suggests that an NT-enriched microenvironment may be favorable for preventing the inflammatory reaction of microglia.

Original languageEnglish
Pages (from-to)666-676
Number of pages11
JournalJournal of Neuroscience Research
Volume81
Issue number5
DOIs
Publication statusPublished - 2005 Sept 1

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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