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...
Gespeichert in:
Veröffentlicht in: | Investigative ophthalmology & visual science 2005-02, Vol.46 (2), p.589-595 |
---|---|
Hauptverfasser: | , , , , , , , |
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 & 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 & 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&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 & 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 & 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 & 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 & 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 & 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 |