Exp Mol Med.  2007 Dec;39(6):812-819.

Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo

• Park KW
• Lee HG
• Jin BK
• Lee YB

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.

Keyword

inflammation; interleukin-10; lipopolysaccharide; microglia; NADPH oxidase; neuron; reactive oxygen species

MeSH Terms

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