PMID- 16723471 OWN - NLM STAT- MEDLINE DCOM- 20060703 LR - 20220317 IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 47 IP - 6 DP - 2006 Jun TI - Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats. PG - 2562-8 AB - PURPOSE: Lutein deposits in the macula and lens of human eyes with high concentration and is well known as an eye-protective nutrient for its beneficial effects on eye disease such as age-related macular degeneration and cataract. The purpose of the present study was to investigate the effects of lutein on endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in male Lewis rats by subcutaneous injection of 200 microg lipopolysaccharide. Lutein or dexamethasone was administered intravenously at 30 minutes before, at the same time as, and at 30 minutes after LPS treatment. The aqueous humor was collected at 24 hours after LPS injection, the number of infiltrating cells, the protein concentration, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, prostaglandin (PG)-E2, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-2 in the aqueous humor were determined. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappaB was performed to evaluate the effect of lutein on NF-kappaB activation in the iris-ciliary body (ICB) of rats. A mouse macrophage cell line (RAW264.7 cells) was stimulated with LPS in the presence or absence of lutein. Expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and degradation of inhibitor kappaB (IkappaB) were analyzed by Western blot analysis. RESULTS: Lutein suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg lutein was as strong as that of 1 mg/kg dexamethasone. Treatment with lutein reduced the concentrations of NO, TNF-alpha, IL-6, PGE2, MCP-1, and MIP-2 in aqueous humor. Lutein also suppressed the activation of NF-kappaB in the ICB as well as iNOS and COX-2 expression and IkappaB degradation in RAW cells. CONCLUSIONS: These findings indicate that lutein has anti-inflammatory effects on EIU by inhibiting the NF-kappaB dependent signaling pathway and the subsequent production of proinflammatory mediators. FAU - Jin, Xue-Hai AU - Jin XH AD - Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. FAU - Ohgami, Kazuhiro AU - Ohgami K FAU - Shiratori, Kenji AU - Shiratori K FAU - Suzuki, Yukari AU - Suzuki Y FAU - Hirano, Takeshi AU - Hirano T FAU - Koyama, Yoshikazu AU - Koyama Y FAU - Yoshida, Kazuhiko AU - Yoshida K FAU - Ilieva, Iliyana AU - Ilieva I FAU - Iseki, Ken AU - Iseki K FAU - Ohno, Shigeaki AU - Ohno S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (I-kappa B Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - X72A60C9MT (Lutein) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Aqueous Humor/metabolism MH - Blotting, Western MH - Cell Line MH - Ciliary Body/drug effects/metabolism MH - Cyclooxygenase 2/metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - I-kappa B Proteins/metabolism MH - Iris/drug effects/metabolism MH - Lipopolysaccharides MH - Lutein/*pharmacology MH - Macrophages/metabolism MH - Male MH - Mice MH - Microscopy, Confocal MH - NF-kappa B/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Rats MH - Rats, Inbred Lew MH - Salmonella typhimurium MH - Uveitis, Anterior/metabolism/*prevention & control EDAT- 2006/05/26 09:00 MHDA- 2006/07/04 09:00 CRDT- 2006/05/26 09:00 PHST- 2006/05/26 09:00 [pubmed] PHST- 2006/07/04 09:00 [medline] PHST- 2006/05/26 09:00 [entrez] AID - 47/6/2562 [pii] AID - 10.1167/iovs.05-1429 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2562-8. doi: 10.1167/iovs.05-1429.