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Neuroprotective role of microglia expressing interleukin‐4
Author(s) -
Park K.W.,
Lee D.Y.,
Joe E.H.,
Kim S.U.,
Jin B.K.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20483
Subject(s) - microglia , tunel assay , neuroprotection , immunostaining , tumor necrosis factor alpha , in vivo , programmed cell death , biology , terminal deoxynucleotidyl transferase , inflammation , microbiology and biotechnology , apoptosis , immunology , immunohistochemistry , neuroscience , biochemistry
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)‐α 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. © 2005 Wiley‐Liss, Inc.