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Neuroprotective role of microglia expressing interleukin-4.

Park, KW; Lee, DY; Joe, EH; Kim, SU; Jin, BK
Journal of neuroscience research, 81(3):397-402, 2005
Journal Title
Journal of neuroscience research
Little is known about the underlying mechanisms responsible for the death of activated microglia and the functional consequences of the death of these cells, especially in vivo. We show here that intracortical injection of lipopolysaccharide (LPS) led to upregulation of interleukin-4 (IL-4) immunoreactivity, followed by a substantial loss of microglia 3 days later, as visualized by complement receptor type 3 (OX-42) immunostaining and tomato lectin staining. Cells positive for caspase-3 and terminal deoxynucleotidyl transferase mediated fluorescein-dUTP nick-end labeling (TUNEL) were also localized within LPS-activated microglia. IL-4 immunoreactivity was detected as early as 12 hr post-LPS, disappearing at 72 hr. Surprisingly, IL-4 immunoreactivity was detected exclusively in microglia, but not in astrocytes or neurons. In addition, IL-4-neutralizing antibodies markedly increased the survival of activated microglia at 3 days post-LPS. The expression of inducible nitric oxide synthase (iNOS) and tumor-necrosis factor (TNF)-alpha was sustained in parallel in activated microglia, consequently increasing neuronal cell death. To our knowledge, this study is the first to show the endogenous expression of IL-4 in LPS-activated microglia in vivo. Our findings suggest that IL-4 may regulate brain inflammation by inducing the death of activated microglia in vivo and increasing neuronal survival.
MeSH terms
Analysis of VarianceAnimalsAntibodies/pharmacologyAntigens, CD11b/metabolismCerebral Cortex/drug effectsCerebral Cortex/pathology*Drug InteractionsFunctional LateralityGene Expression Regulation/drug effectsImmunohistochemistry/methodsIn Situ Nick-End Labeling/methodsInterleukin-4/physiology*Lipopolysaccharides/pharmacologyMicroglia/drug effectsMicroglia/metabolism*Neurons/drug effectsNeurons/metabolism*Neuroprotective AgentsNitric Oxide Synthase/geneticsNitric Oxide Synthase/metabolismNitric Oxide Synthase Type IIPhosphopyruvate Hydratase/metabolismPlant Lectins/metabolismRNA, Messenger/metabolismRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain Reaction/methodsTime FactorsTumor Necrosis Factor-alpha/geneticsTumor Necrosis Factor-alpha/metabolism
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
조, 은혜김, 승업진, 병관
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