Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats.
OBJECTIVE
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.
Jin
Xue-Hai
XH
Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Ohgami
Kazuhiro
K
Shiratori
Kenji
K
Suzuki
Yukari
Y
Hirano
Takeshi
T
Koyama
Yoshikazu
Y
Yoshida
Kazuhiko
K
Ilieva
Iliyana
I
Iseki
Ken
K
Ohno
Shigeaki
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020672:I-kappa B Proteins / Q000378:metabolism; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D014975:Lutein / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D014606:Uveitis, Anterior / Q000378:metabolism / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D014975:Lutein