Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis
To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU). Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expre...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2007-04, Vol.48 (4), p.1711-1717 |
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| creator | Chang, John H Hampartzoumian, Taline Everett, Beth Lloyd, Andrew McCluskey, Peter J Wakefield, Denis |
| description | To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU).
Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16(+) neutrophils and CD14(+) monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR.
A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-gamma production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1beta in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation.
There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU. |
| doi_str_mv | 10.1167/iovs.06-0807 |
| format | Article |
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Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16(+) neutrophils and CD14(+) monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR.
A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-gamma production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1beta in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation.
There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.06-0807</identifier><identifier>PMID: 17389503</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Acute Disease ; Adult ; Biological and medical sciences ; Cytokines - metabolism ; Eye and associated structures. Visual pathways and centers. Vision ; Female ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Genotype ; Humans ; Lipopolysaccharide Receptors - metabolism ; Lipopolysaccharides - pharmacology ; Male ; Medical sciences ; Monocytes - drug effects ; Monocytes - metabolism ; Neutrophils - drug effects ; Neutrophils - metabolism ; Ophthalmology ; Peptidoglycan - pharmacology ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, IgG - metabolism ; Toll-Like Receptor 2 - genetics ; Toll-Like Receptor 2 - metabolism ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - metabolism ; Uvea diseases ; Uveitis, Anterior - blood ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology & visual science, 2007-04, Vol.48 (4), p.1711-1717</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-c083cc68af9e5fc08fe4ac60ae9c3b0122e77824303cd06825f599f37e4946903</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18652921$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17389503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, John H</creatorcontrib><creatorcontrib>Hampartzoumian, Taline</creatorcontrib><creatorcontrib>Everett, Beth</creatorcontrib><creatorcontrib>Lloyd, Andrew</creatorcontrib><creatorcontrib>McCluskey, Peter J</creatorcontrib><creatorcontrib>Wakefield, Denis</creatorcontrib><title>Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU).
Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16(+) neutrophils and CD14(+) monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR.
A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-gamma production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1beta in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation.
There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU.</description><subject>Acute Disease</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cytokines - metabolism</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genotype</subject><subject>Humans</subject><subject>Lipopolysaccharide Receptors - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>Ophthalmology</subject><subject>Peptidoglycan - pharmacology</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Receptors, IgG - metabolism</subject><subject>Toll-Like Receptor 2 - genetics</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Uvea diseases</subject><subject>Uveitis, Anterior - blood</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>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1vEzEQxS0Eomnhxhn5AgKJLf7YD-8xilpAigBV6dlynNmuwbsOHm-X_gX9t3FopJxm3tNPb0aPkDecXXJeN59duMdLVhdMseYZWfCqEkXVKPmcLBgvs1-y8oycI_5iTHAu2Etyxhup2orJBXlc9Wa8A6RupJvgfeHdb6A3YGGfQqQfNuubj4WgZtzRvJb06u8-AqIL43_vehptOojtlOj3kOjP4B-GEPe9wwHpMgJdIgbrTIIdnV3q6dJOKbtjgujyhdt7cMnhK_KiMx7h9XFekNvrq83qa7H-8eXbarkurFQqFZYpaW2tTNdC1WXVQWlszQy0Vm4ZFwKaRolSMml3rFai6qq27WQDZVvWLZMX5P1T7j6GPxNg0oNDC96bEcKEumGS80qIDH56Am0MiBE6vY9uMPFBc6YPxetD8ZrV-lB8xt8ec6ftALsTfGw6A--OgEFrfBfNaB2eOFVXohX89GDv7vrZRdA4GO9zLNfzPJdKlzmUc_kP9TqY5w</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Chang, John H</creator><creator>Hampartzoumian, Taline</creator><creator>Everett, Beth</creator><creator>Lloyd, Andrew</creator><creator>McCluskey, Peter J</creator><creator>Wakefield, Denis</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>20070401</creationdate><title>Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis</title><author>Chang, John H ; Hampartzoumian, Taline ; Everett, Beth ; Lloyd, Andrew ; McCluskey, Peter J ; Wakefield, Denis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-c083cc68af9e5fc08fe4ac60ae9c3b0122e77824303cd06825f599f37e4946903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acute Disease</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cytokines - metabolism</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genotype</topic><topic>Humans</topic><topic>Lipopolysaccharide Receptors - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>Ophthalmology</topic><topic>Peptidoglycan - pharmacology</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Receptors, IgG - metabolism</topic><topic>Toll-Like Receptor 2 - genetics</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Toll-Like Receptor 4 - genetics</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Uvea diseases</topic><topic>Uveitis, Anterior - blood</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, John H</creatorcontrib><creatorcontrib>Hampartzoumian, Taline</creatorcontrib><creatorcontrib>Everett, Beth</creatorcontrib><creatorcontrib>Lloyd, Andrew</creatorcontrib><creatorcontrib>McCluskey, Peter J</creatorcontrib><creatorcontrib>Wakefield, Denis</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>Chang, John H</au><au>Hampartzoumian, Taline</au><au>Everett, Beth</au><au>Lloyd, Andrew</au><au>McCluskey, Peter J</au><au>Wakefield, Denis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>48</volume><issue>4</issue><spage>1711</spage><epage>1717</epage><pages>1711-1717</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU).
Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16(+) neutrophils and CD14(+) monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR.
A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-gamma production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1beta in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation.
There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>17389503</pmid><doi>10.1167/iovs.06-0807</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0146-0404 |
| ispartof | Investigative ophthalmology & visual science, 2007-04, Vol.48 (4), p.1711-1717 |
| issn | 0146-0404 1552-5783 1552-5783 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Acute Disease Adult Biological and medical sciences Cytokines - metabolism Eye and associated structures. Visual pathways and centers. Vision Female Flow Cytometry Fundamental and applied biological sciences. Psychology Genotype Humans Lipopolysaccharide Receptors - metabolism Lipopolysaccharides - pharmacology Male Medical sciences Monocytes - drug effects Monocytes - metabolism Neutrophils - drug effects Neutrophils - metabolism Ophthalmology Peptidoglycan - pharmacology Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Restriction Fragment Length Receptors, IgG - metabolism Toll-Like Receptor 2 - genetics Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - metabolism Uvea diseases Uveitis, Anterior - blood Vertebrates: nervous system and sense organs |
| title | Changes in Toll-like Receptor (TLR)-2 and TLR4 Expression and Function but Not Polymorphisms Are Associated with Acute Anterior Uveitis |
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