Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation

Toll-like receptors (TLRs), which recognize microbial products, have an important role in the host innate immune response. The purpose of the present study was to determine whether activation of these receptors leads to development of keratitis and to assess the role of the common adaptor molecule m...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Investigative ophthalmology & visual science 2005-02, Vol.46 (2), p.589-595
Hauptverfasser: Johnson, Angela C, Heinzel, Fred P, Diaconu, Eugenia, Sun, Yan, Hise, Amy G, Golenbock, Douglas, Lass, Jonathan H, Pearlman, Eric
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 595
container_issue 2
container_start_page 589
container_title Investigative ophthalmology & visual science
container_volume 46
creator Johnson, Angela C
Heinzel, Fred P
Diaconu, Eugenia
Sun, Yan
Hise, Amy G
Golenbock, Douglas
Lass, Jonathan H
Pearlman, Eric
description Toll-like receptors (TLRs), which recognize microbial products, have an important role in the host innate immune response. The purpose of the present study was to determine whether activation of these receptors leads to development of keratitis and to assess the role of the common adaptor molecule myeloid differentiation factor-88 (MyD88). Corneal epithelium of C57BL/6, TLR2(-/-), TLR9(-/-), and MyD88(-/-) mice was abraded and treated with Pam(3)Cys, LPS, or CpG DNA, which bind TLR2, -4, and -9, respectively, and neutrophil recruitment to the corneal stroma, development of corneal haze, and chemokine production were measured. Activation of TLR2 and -9 stimulated neutrophil recruitment to the corneal stroma of C57BL/6 mice, but not TLR2(-/-) or -9(-/-) mice, respectively. In marked contrast, neutrophil migration to the corneal stroma of MyD88(-/-) mice challenged with Pam(3)Cys, LPS, or CpG DNA was completely ablated. Activation of TLR2, -4, and -9 also caused a significant increase in corneal thickness and haze, indicative of disruption of corneal clarity; however, this response was ablated in MyD88(-/-) mice, which were not significantly different from untreated corneas. Production of CXC chemokines MIP-2 and KC, which mediate neutrophil recruitment to the corneal stroma, was elevated in the corneal epithelium and stroma of control, but not MyD88(-/-) mice. Together, these findings demonstrate that the corneal epithelium has functional TLR2 and -9, and that TLR2, -4, and -9 signal through MyD88. This pathway is therefore likely to have an important role in the early events leading to microbial keratitis.
doi_str_mv 10.1167/iovs.04-1077
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67385928</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67385928</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-2c4600a9235b9627e07f09624c18fa4ec14d0d7d8b43d1dbd9e424b991f68d283</originalsourceid><addsrcrecordid>eNpNkF1rFDEUhoModq3eeS25URR2apLJJJnLsvWjsEUo63XIJGfcaCZZk9kuBX-8M3agXp0XznPeAw9Crym5oFTIjz7dlQvCK0qkfIJWtGlY1UhVP0UrQrmoCCf8DL0o5SchjFJGnqMz2ghJmRIr9OfSjv7OjD5FnHq8SyFUW_8L8C1YOIwp4_e77e0HtsbT4GtsoptTi33E4x7wjRkGE7yJeJNyBIOvoztaKPjm_kqp6goOEB3EcVmHad-H-Wb--BI9600o8GqZ5-j750-7zddq--3L9eZyW1ne1GPFLBeEmJbVTdcKJoHInkyBW6p6w8FS7oiTTnW8dtR1rgXOeNe2tBfKMVWfo3cPvYecfh-hjHrwxUIIJkI6Fi1krZr2H7h-AG1OpWTo9SH7weR7TYmebevZtiZcz7Yn_M3Se-wGcI_woncC3i6AKdaEPptofXnkBG-Eqv_j9v7H_uQz6DJZDVMt1afTiQvNdKPa-i9Jj5Lz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67385928</pqid></control><display><type>article</type><title>Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Johnson, Angela C ; Heinzel, Fred P ; Diaconu, Eugenia ; Sun, Yan ; Hise, Amy G ; Golenbock, Douglas ; Lass, Jonathan H ; Pearlman, Eric</creator><creatorcontrib>Johnson, Angela C ; Heinzel, Fred P ; Diaconu, Eugenia ; Sun, Yan ; Hise, Amy G ; Golenbock, Douglas ; Lass, Jonathan H ; Pearlman, Eric</creatorcontrib><description>Toll-like receptors (TLRs), which recognize microbial products, have an important role in the host innate immune response. The purpose of the present study was to determine whether activation of these receptors leads to development of keratitis and to assess the role of the common adaptor molecule myeloid differentiation factor-88 (MyD88). Corneal epithelium of C57BL/6, TLR2(-/-), TLR9(-/-), and MyD88(-/-) mice was abraded and treated with Pam(3)Cys, LPS, or CpG DNA, which bind TLR2, -4, and -9, respectively, and neutrophil recruitment to the corneal stroma, development of corneal haze, and chemokine production were measured. Activation of TLR2 and -9 stimulated neutrophil recruitment to the corneal stroma of C57BL/6 mice, but not TLR2(-/-) or -9(-/-) mice, respectively. In marked contrast, neutrophil migration to the corneal stroma of MyD88(-/-) mice challenged with Pam(3)Cys, LPS, or CpG DNA was completely ablated. Activation of TLR2, -4, and -9 also caused a significant increase in corneal thickness and haze, indicative of disruption of corneal clarity; however, this response was ablated in MyD88(-/-) mice, which were not significantly different from untreated corneas. Production of CXC chemokines MIP-2 and KC, which mediate neutrophil recruitment to the corneal stroma, was elevated in the corneal epithelium and stroma of control, but not MyD88(-/-) mice. Together, these findings demonstrate that the corneal epithelium has functional TLR2 and -9, and that TLR2, -4, and -9 signal through MyD88. This pathway is therefore likely to have an important role in the early events leading to microbial keratitis.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.04-1077</identifier><identifier>PMID: 15671286</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Adaptor Proteins, Signal Transducing ; Animals ; Antigens, Differentiation - physiology ; Biological and medical sciences ; Chemokines, CXC - metabolism ; Corneal Stroma - immunology ; CpG Islands ; Cysteine - analogs &amp; derivatives ; Cysteine - pharmacology ; Diseases of cornea, anterior segment and sclera ; DNA-Binding Proteins - metabolism ; Epithelium, Corneal - drug effects ; Epithelium, Corneal - metabolism ; Fluorescent Antibody Technique, Indirect ; Keratitis - metabolism ; Lipopolysaccharides - pharmacology ; Lipoproteins - pharmacology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88 ; Neutrophil Infiltration ; Neutrophils - immunology ; Ophthalmology ; Receptors, Cell Surface - metabolism ; Receptors, Immunologic - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Toll-Like Receptor 9</subject><ispartof>Investigative ophthalmology &amp; visual science, 2005-02, Vol.46 (2), p.589-595</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-2c4600a9235b9627e07f09624c18fa4ec14d0d7d8b43d1dbd9e424b991f68d283</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&amp;idt=16456836$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15671286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Johnson, Angela C</creatorcontrib><creatorcontrib>Heinzel, Fred P</creatorcontrib><creatorcontrib>Diaconu, Eugenia</creatorcontrib><creatorcontrib>Sun, Yan</creatorcontrib><creatorcontrib>Hise, Amy G</creatorcontrib><creatorcontrib>Golenbock, Douglas</creatorcontrib><creatorcontrib>Lass, Jonathan H</creatorcontrib><creatorcontrib>Pearlman, Eric</creatorcontrib><title>Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation</title><title>Investigative ophthalmology &amp; visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Toll-like receptors (TLRs), which recognize microbial products, have an important role in the host innate immune response. The purpose of the present study was to determine whether activation of these receptors leads to development of keratitis and to assess the role of the common adaptor molecule myeloid differentiation factor-88 (MyD88). Corneal epithelium of C57BL/6, TLR2(-/-), TLR9(-/-), and MyD88(-/-) mice was abraded and treated with Pam(3)Cys, LPS, or CpG DNA, which bind TLR2, -4, and -9, respectively, and neutrophil recruitment to the corneal stroma, development of corneal haze, and chemokine production were measured. Activation of TLR2 and -9 stimulated neutrophil recruitment to the corneal stroma of C57BL/6 mice, but not TLR2(-/-) or -9(-/-) mice, respectively. In marked contrast, neutrophil migration to the corneal stroma of MyD88(-/-) mice challenged with Pam(3)Cys, LPS, or CpG DNA was completely ablated. Activation of TLR2, -4, and -9 also caused a significant increase in corneal thickness and haze, indicative of disruption of corneal clarity; however, this response was ablated in MyD88(-/-) mice, which were not significantly different from untreated corneas. Production of CXC chemokines MIP-2 and KC, which mediate neutrophil recruitment to the corneal stroma, was elevated in the corneal epithelium and stroma of control, but not MyD88(-/-) mice. Together, these findings demonstrate that the corneal epithelium has functional TLR2 and -9, and that TLR2, -4, and -9 signal through MyD88. This pathway is therefore likely to have an important role in the early events leading to microbial keratitis.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Animals</subject><subject>Antigens, Differentiation - physiology</subject><subject>Biological and medical sciences</subject><subject>Chemokines, CXC - metabolism</subject><subject>Corneal Stroma - immunology</subject><subject>CpG Islands</subject><subject>Cysteine - analogs &amp; derivatives</subject><subject>Cysteine - pharmacology</subject><subject>Diseases of cornea, anterior segment and sclera</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Epithelium, Corneal - drug effects</subject><subject>Epithelium, Corneal - metabolism</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Keratitis - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lipoproteins - pharmacology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myeloid Differentiation Factor 88</subject><subject>Neutrophil Infiltration</subject><subject>Neutrophils - immunology</subject><subject>Ophthalmology</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Immunologic - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-Like Receptor 4</subject><subject>Toll-Like Receptor 9</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkF1rFDEUhoModq3eeS25URR2apLJJJnLsvWjsEUo63XIJGfcaCZZk9kuBX-8M3agXp0XznPeAw9Crym5oFTIjz7dlQvCK0qkfIJWtGlY1UhVP0UrQrmoCCf8DL0o5SchjFJGnqMz2ghJmRIr9OfSjv7OjD5FnHq8SyFUW_8L8C1YOIwp4_e77e0HtsbT4GtsoptTi33E4x7wjRkGE7yJeJNyBIOvoztaKPjm_kqp6goOEB3EcVmHad-H-Wb--BI9600o8GqZ5-j750-7zddq--3L9eZyW1ne1GPFLBeEmJbVTdcKJoHInkyBW6p6w8FS7oiTTnW8dtR1rgXOeNe2tBfKMVWfo3cPvYecfh-hjHrwxUIIJkI6Fi1krZr2H7h-AG1OpWTo9SH7weR7TYmebevZtiZcz7Yn_M3Se-wGcI_woncC3i6AKdaEPptofXnkBG-Eqv_j9v7H_uQz6DJZDVMt1afTiQvNdKPa-i9Jj5Lz</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Johnson, Angela C</creator><creator>Heinzel, Fred P</creator><creator>Diaconu, Eugenia</creator><creator>Sun, Yan</creator><creator>Hise, Amy G</creator><creator>Golenbock, Douglas</creator><creator>Lass, Jonathan H</creator><creator>Pearlman, Eric</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>20050201</creationdate><title>Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation</title><author>Johnson, Angela C ; Heinzel, Fred P ; Diaconu, Eugenia ; Sun, Yan ; Hise, Amy G ; Golenbock, Douglas ; Lass, Jonathan H ; Pearlman, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-2c4600a9235b9627e07f09624c18fa4ec14d0d7d8b43d1dbd9e424b991f68d283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Animals</topic><topic>Antigens, Differentiation - physiology</topic><topic>Biological and medical sciences</topic><topic>Chemokines, CXC - metabolism</topic><topic>Corneal Stroma - immunology</topic><topic>CpG Islands</topic><topic>Cysteine - analogs &amp; derivatives</topic><topic>Cysteine - pharmacology</topic><topic>Diseases of cornea, anterior segment and sclera</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Epithelium, Corneal - drug effects</topic><topic>Epithelium, Corneal - metabolism</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Keratitis - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Lipoproteins - pharmacology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myeloid Differentiation Factor 88</topic><topic>Neutrophil Infiltration</topic><topic>Neutrophils - immunology</topic><topic>Ophthalmology</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Immunologic - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Toll-Like Receptor 2</topic><topic>Toll-Like Receptor 4</topic><topic>Toll-Like Receptor 9</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Johnson, Angela C</creatorcontrib><creatorcontrib>Heinzel, Fred P</creatorcontrib><creatorcontrib>Diaconu, Eugenia</creatorcontrib><creatorcontrib>Sun, Yan</creatorcontrib><creatorcontrib>Hise, Amy G</creatorcontrib><creatorcontrib>Golenbock, Douglas</creatorcontrib><creatorcontrib>Lass, Jonathan H</creatorcontrib><creatorcontrib>Pearlman, Eric</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 &amp; visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Johnson, Angela C</au><au>Heinzel, Fred P</au><au>Diaconu, Eugenia</au><au>Sun, Yan</au><au>Hise, Amy G</au><au>Golenbock, Douglas</au><au>Lass, Jonathan H</au><au>Pearlman, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation</atitle><jtitle>Investigative ophthalmology &amp; visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>46</volume><issue>2</issue><spage>589</spage><epage>595</epage><pages>589-595</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>Toll-like receptors (TLRs), which recognize microbial products, have an important role in the host innate immune response. The purpose of the present study was to determine whether activation of these receptors leads to development of keratitis and to assess the role of the common adaptor molecule myeloid differentiation factor-88 (MyD88). Corneal epithelium of C57BL/6, TLR2(-/-), TLR9(-/-), and MyD88(-/-) mice was abraded and treated with Pam(3)Cys, LPS, or CpG DNA, which bind TLR2, -4, and -9, respectively, and neutrophil recruitment to the corneal stroma, development of corneal haze, and chemokine production were measured. Activation of TLR2 and -9 stimulated neutrophil recruitment to the corneal stroma of C57BL/6 mice, but not TLR2(-/-) or -9(-/-) mice, respectively. In marked contrast, neutrophil migration to the corneal stroma of MyD88(-/-) mice challenged with Pam(3)Cys, LPS, or CpG DNA was completely ablated. Activation of TLR2, -4, and -9 also caused a significant increase in corneal thickness and haze, indicative of disruption of corneal clarity; however, this response was ablated in MyD88(-/-) mice, which were not significantly different from untreated corneas. Production of CXC chemokines MIP-2 and KC, which mediate neutrophil recruitment to the corneal stroma, was elevated in the corneal epithelium and stroma of control, but not MyD88(-/-) mice. Together, these findings demonstrate that the corneal epithelium has functional TLR2 and -9, and that TLR2, -4, and -9 signal through MyD88. This pathway is therefore likely to have an important role in the early events leading to microbial keratitis.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>15671286</pmid><doi>10.1167/iovs.04-1077</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0146-0404
ispartof Investigative ophthalmology & visual science, 2005-02, Vol.46 (2), p.589-595
issn 0146-0404
1552-5783
1552-5783
language eng
recordid cdi_proquest_miscellaneous_67385928
source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Adaptor Proteins, Signal Transducing
Animals
Antigens, Differentiation - physiology
Biological and medical sciences
Chemokines, CXC - metabolism
Corneal Stroma - immunology
CpG Islands
Cysteine - analogs & derivatives
Cysteine - pharmacology
Diseases of cornea, anterior segment and sclera
DNA-Binding Proteins - metabolism
Epithelium, Corneal - drug effects
Epithelium, Corneal - metabolism
Fluorescent Antibody Technique, Indirect
Keratitis - metabolism
Lipopolysaccharides - pharmacology
Lipoproteins - pharmacology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Neutrophil Infiltration
Neutrophils - immunology
Ophthalmology
Receptors, Cell Surface - metabolism
Receptors, Immunologic - physiology
Reverse Transcriptase Polymerase Chain Reaction
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 9
title Activation of Toll-Like Receptor (TLR)2, TLR4, and TLR9 in the Mammalian Cornea Induces MyD88-Dependent Corneal Inflammation
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T05%3A05%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activation%20of%20Toll-Like%20Receptor%20(TLR)2,%20TLR4,%20and%20TLR9%20in%20the%20Mammalian%20Cornea%20Induces%20MyD88-Dependent%20Corneal%20Inflammation&rft.jtitle=Investigative%20ophthalmology%20&%20visual%20science&rft.au=Johnson,%20Angela%20C&rft.date=2005-02-01&rft.volume=46&rft.issue=2&rft.spage=589&rft.epage=595&rft.pages=589-595&rft.issn=0146-0404&rft.eissn=1552-5783&rft.coden=IOVSDA&rft_id=info:doi/10.1167/iovs.04-1077&rft_dat=%3Cproquest_cross%3E67385928%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67385928&rft_id=info:pmid/15671286&rfr_iscdi=true