Microglia expressing interleukin-13 undergo cell death and contribute to neuronal survival in vivo.
How to minimize brain inflammation is pathophysiologically important, since inflammation induced by microglial activation can exacerbate brain damage. In the present report, we show that injection of lipopolysaccharide (LPS) into the rat cortex led to increased levels of interleukin-13 (IL-13) and to IL-13 immunoreactivity, followed by the substantial loss of microglia at 3 days post-LPS. IL-13 levels in LPS-injected cortex reached a peak at 12 h post-injection, remained elevated at 24 h, and returned to basal levels at day 4. In parallel, IL-13 immunoreactivity was detected as early as 12 h post-LPS and maintained up to 24 h; it disappeared at 4 days. Surprisingly, IL-13 immunoreactivity was detected exclusively in microglia, but not in neurons or astrocytes. Following treatment with LPS in vitro, IL-13 expression was also induced in microglia in the presence of neurons, but not in the presence of astrocytes or in cultured pure microglia alone. In experiments designed to determine the involvement of IL-13 in microglia cell death, IL-13-neutralizing antibodies significantly increased survival of activated microglia at 3 days post-LPS. Consistent with these results, the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was sustained in activated microglia and neuronal cell death was consequently increased. Taken together, the present study is the first to demonstrate the endogenous expression of IL-13 in LPS-activated microglia in vivo, and to demonstrate that neurons may be required for IL-13 expression in microglia. Our data strongly suggest that IL-13 may control brain inflammation by inducing the death of activated microglia in vivo, resulting in an enhancement of neuronal survival.
Shin
Won Ho
WH
Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea.
Lee
Da-Yong
DY
Park
Keun Woo
KW
Kim
Seung Up
SU
Yang
Myung-Soon
MS
Joe
Eun-Hye
EH
Jin
Byung Kwan
BK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D015870:Gene Expression; D018793:Interleukin-13 / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology* / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000906:Antibodies; D018793:Interleukin-13; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat