PMID- 18160852 OWN - NLM STAT- MEDLINE DCOM- 20080506 LR - 20071227 IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 39 IP - 6 DP - 2007 Dec 31 TI - Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo. PG - 812-9 AB - 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. FAU - Park, Keun Woo AU - Park KW AD - Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-721, Korea. FAU - Lee, Hwan Goo AU - Lee HG FAU - Jin, Byung Kwan AU - Jin BK FAU - Lee, Yong Beom AU - Lee YB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Lipopolysaccharides) RN - 0 (Reactive Oxygen Species) RN - 130068-27-8 (Interleukin-10) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Animals MH - Cerebral Cortex/drug effects/*pathology MH - Fluorescent Antibody Technique MH - Interleukin-10/immunology/*physiology MH - Lipopolysaccharides/*pharmacology MH - Microglia/cytology/*metabolism MH - Nerve Degeneration/pathology/*prevention & control MH - Neurons/cytology/drug effects/*metabolism MH - Nitric Oxide Synthase/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism EDAT- 2007/12/28 09:00 MHDA- 2008/05/07 09:00 CRDT- 2007/12/28 09:00 PHST- 2007/12/28 09:00 [pubmed] PHST- 2008/05/07 09:00 [medline] PHST- 2007/12/28 09:00 [entrez] AID - 2007123115 [pii] AID - 10.1038/emm.2007.88 [doi] PST - ppublish SO - Exp Mol Med. 2007 Dec 31;39(6):812-9. doi: 10.1038/emm.2007.88.