Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo.
- Author:
Keun Woo PARK
1
;
Hwan Goo LEE
;
Byung Kwan JIN
;
Yong Beom LEE
Author Information
1. Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-721, Korea. yblee@ajou.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
inflammation;
interleukin-10;
lipopolysaccharide;
microglia;
NADPH oxidase;
neuron;
reactive oxygen species
- MeSH:
Animals;
Cerebral Cortex/drug effects/*pathology;
Fluorescent Antibody Technique;
Interleukin-10/immunology/*physiology;
Lipopolysaccharides/*pharmacology;
Microglia/cytology/*metabolism;
Nerve Degeneration/pathology/*prevention & control;
Neurons/cytology/drug effects/*metabolism;
Nitric Oxide Synthase/genetics/metabolism;
Rats;
Rats, Sprague-Dawley;
Reactive Oxygen Species/metabolism
- From:Experimental & Molecular Medicine
2007;39(6):812-819
- CountryRepublic of Korea
- Language:English
-
Abstract:
A degree of brain inflammation is required for repair of damaged tissue, but excessive inflammation causes neuronal cell death. Here, we observe that IL-10 is expressed in LPS-injected rat cerebral cortex, contributing to neuronal survival. Cells immunopositive for IL-10 were detected as early as 8 h post-injection and persisted for up to 3 d, in parallel with the expression of IL-1beta, TNF-alpha, and iNOS. Double immunofluorescence staining showed that IL-10 expression was localized mainly in activated microglia. Next, we examined the neuroprotective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action caused a significant loss of neurons both 3 d and 7 d after LPS injection. Further, the induction of mRNA species encoding IL-1beta, TNF-alpha, and iNOS, reactive oxygen species (ROS) production, and NADPH oxidase activation, increased after co-injection of LPS and IL-10NA, compared to the levels seen after injection of LPS alone. Taken together, these results clearly suggest that LPS-induced endogenous expression of IL-10 in microglia contributes to neuronal survival by inhibiting brain inflammation.
