Microglia expressing interleukin-13 undergo cell death and contribute to neuronal survival in vivo

• Published in: Glia Vol. 46; no. 2; pp. 142 - 152
• Main Authors: Shin, Won Ho, Lee, Da-Yong, Park, Keun Woo, Kim, Seung Up, Yang, Myung-Soon, Joe, Eun-Hye, Jin, Byung Kwan
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2004; Wiley-Liss
• Subjects: Animals; Antibodies - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Cell Communication - physiology; Cell Survival - physiology; Cells, Cultured; Cerebral Cortex - cytology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; inducible nitric oxide; interleukin-13; Interleukin-13 - genetics; Interleukin-13 - immunology; Isolated neuron and nerve. Neuroglia; lipopolysaccharide; Lipopolysaccharides - pharmacology; microglia; Microglia - cytology; Microglia - physiology; Neurons - cytology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - genetics; tumor necrosis factor-α; Vertebrates: nervous system and sense organs; Glial cell; Neuroglia; tumor necrosis factor-a; Cytokine; Central nervous system; Interleukin 13; inducible nitric oxide; interleukin-13; Microglia; Tumor necrosis factor; Cell death; Nitric oxide; Lipopolysaccharide; Apoptosis
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.10357

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‐α (TNF‐α) 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. © 2004 Wiley‐Liss, Inc.