Inhibitory Effects of Lutein on Endotoxin-Induced Uveitis in Lewis Rats
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 e...
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| creator | Jin, Xue-Hai Ohgami, Kazuhiro Shiratori, Kenji Suzuki, Yukari Hirano, Takeshi Koyama, Yoshikazu Yoshida, Kazuhiko Ilieva, Iliyana Iseki, Ken Ohno, Shigeaki |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1167/iovs.05-1429 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.05-1429</identifier><identifier>PMID: 16723471</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Aqueous Humor - metabolism ; Biological and medical sciences ; Blotting, Western ; Cell Line ; Ciliary Body - drug effects ; Ciliary Body - metabolism ; Cyclooxygenase 2 - metabolism ; Cytokines - metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Eye and associated structures. Visual pathways and centers. Vision ; Fundamental and applied biological sciences. Psychology ; I-kappa B Proteins - metabolism ; Iris - drug effects ; Iris - metabolism ; Lipopolysaccharides ; Lutein - pharmacology ; Macrophages - metabolism ; Male ; Medical sciences ; Mice ; Microscopy, Confocal ; NF-kappa B - metabolism ; Nitric Oxide Synthase Type II - metabolism ; Ophthalmology ; Rats ; Rats, Inbred Lew ; Salmonella typhimurium ; Uvea diseases ; Uveitis, Anterior - metabolism ; Uveitis, Anterior - prevention & control ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology & visual science, 2006-06, Vol.47 (6), p.2562-2568</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-e803ec15c0c2b3dfe3a18ae46a90d1d0c63ee4efbc4031821d8b271046a503343</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17801529$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16723471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Xue-Hai</creatorcontrib><creatorcontrib>Ohgami, Kazuhiro</creatorcontrib><creatorcontrib>Shiratori, Kenji</creatorcontrib><creatorcontrib>Suzuki, Yukari</creatorcontrib><creatorcontrib>Hirano, Takeshi</creatorcontrib><creatorcontrib>Koyama, Yoshikazu</creatorcontrib><creatorcontrib>Yoshida, Kazuhiko</creatorcontrib><creatorcontrib>Ilieva, Iliyana</creatorcontrib><creatorcontrib>Iseki, Ken</creatorcontrib><creatorcontrib>Ohno, Shigeaki</creatorcontrib><title>Inhibitory Effects of Lutein on Endotoxin-Induced Uveitis in Lewis Rats</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Aqueous Humor - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Ciliary Body - drug effects</subject><subject>Ciliary Body - metabolism</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>I-kappa B Proteins - metabolism</subject><subject>Iris - drug effects</subject><subject>Iris - metabolism</subject><subject>Lipopolysaccharides</subject><subject>Lutein - pharmacology</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microscopy, Confocal</subject><subject>NF-kappa B - metabolism</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Ophthalmology</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Salmonella typhimurium</subject><subject>Uvea diseases</subject><subject>Uveitis, Anterior - metabolism</subject><subject>Uveitis, Anterior - prevention & control</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMoun7cPEsverI6k4-2exRZdWFBED2HNJ26kW6jTWv135vVgqcZmGfeGR7GThGuELP82vnPcAUqRcnnO2yGSvFU5YXYZTNAmaUgQR6wwxDeADgih312EPe4kDnO2P2yXbvS9b77ThZ1TbYPia-T1dCTaxPfJou28r3_cm26bKvBUpW8fJLrXUjifEVjbJ5MH47ZXm2aQCdTPWIvd4vn24d09Xi_vL1ZpVYq2adUgCCLyoLlpahqEgYLQzIzc6iwApsJIkl1aSUILDhWRclzhAgoEEKKI3bxl_ve-Y-BQq83LlhqGtOSH4LOCkAh5vMIXv6BtvMhdFTr985tTPetEfRWnN6K06D0VlzEz6bcodxQ9Q9PpiJwPgEmWNPUnWmtC_9cHg-r36DpwbV7XY-uIx02pmliLOpxHGWuM81VxsUPcmGDCQ</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Jin, Xue-Hai</creator><creator>Ohgami, Kazuhiro</creator><creator>Shiratori, Kenji</creator><creator>Suzuki, Yukari</creator><creator>Hirano, Takeshi</creator><creator>Koyama, Yoshikazu</creator><creator>Yoshida, Kazuhiko</creator><creator>Ilieva, Iliyana</creator><creator>Iseki, Ken</creator><creator>Ohno, Shigeaki</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20060601</creationdate><title>Inhibitory Effects of Lutein on Endotoxin-Induced Uveitis in Lewis Rats</title><author>Jin, Xue-Hai ; Ohgami, Kazuhiro ; Shiratori, Kenji ; Suzuki, Yukari ; Hirano, Takeshi ; Koyama, Yoshikazu ; Yoshida, Kazuhiko ; Ilieva, Iliyana ; Iseki, Ken ; Ohno, Shigeaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-e803ec15c0c2b3dfe3a18ae46a90d1d0c63ee4efbc4031821d8b271046a503343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Aqueous Humor - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Ciliary Body - drug effects</topic><topic>Ciliary Body - metabolism</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>I-kappa B Proteins - metabolism</topic><topic>Iris - drug effects</topic><topic>Iris - metabolism</topic><topic>Lipopolysaccharides</topic><topic>Lutein - pharmacology</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microscopy, Confocal</topic><topic>NF-kappa B - metabolism</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Ophthalmology</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Salmonella typhimurium</topic><topic>Uvea diseases</topic><topic>Uveitis, Anterior - metabolism</topic><topic>Uveitis, Anterior - prevention & control</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Xue-Hai</creatorcontrib><creatorcontrib>Ohgami, Kazuhiro</creatorcontrib><creatorcontrib>Shiratori, Kenji</creatorcontrib><creatorcontrib>Suzuki, Yukari</creatorcontrib><creatorcontrib>Hirano, Takeshi</creatorcontrib><creatorcontrib>Koyama, Yoshikazu</creatorcontrib><creatorcontrib>Yoshida, Kazuhiko</creatorcontrib><creatorcontrib>Ilieva, Iliyana</creatorcontrib><creatorcontrib>Iseki, Ken</creatorcontrib><creatorcontrib>Ohno, Shigeaki</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Xue-Hai</au><au>Ohgami, Kazuhiro</au><au>Shiratori, Kenji</au><au>Suzuki, Yukari</au><au>Hirano, Takeshi</au><au>Koyama, Yoshikazu</au><au>Yoshida, Kazuhiko</au><au>Ilieva, Iliyana</au><au>Iseki, Ken</au><au>Ohno, Shigeaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory Effects of Lutein on Endotoxin-Induced Uveitis in Lewis Rats</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>47</volume><issue>6</issue><spage>2562</spage><epage>2568</epage><pages>2562-2568</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>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.
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.
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.
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.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>16723471</pmid><doi>10.1167/iovs.05-1429</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Aqueous Humor - metabolism Biological and medical sciences Blotting, Western Cell Line Ciliary Body - drug effects Ciliary Body - metabolism Cyclooxygenase 2 - metabolism Cytokines - metabolism Disease Models, Animal Dose-Response Relationship, Drug Eye and associated structures. Visual pathways and centers. Vision Fundamental and applied biological sciences. Psychology I-kappa B Proteins - metabolism Iris - drug effects Iris - metabolism Lipopolysaccharides Lutein - pharmacology Macrophages - metabolism Male Medical sciences Mice Microscopy, Confocal NF-kappa B - metabolism Nitric Oxide Synthase Type II - metabolism Ophthalmology Rats Rats, Inbred Lew Salmonella typhimurium Uvea diseases Uveitis, Anterior - metabolism Uveitis, Anterior - prevention & control Vertebrates: nervous system and sense organs |
| title | Inhibitory Effects of Lutein on Endotoxin-Induced Uveitis in Lewis Rats |
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