ChloroquineV1, Main, Exploration, bibRecord, 001021

Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.

Identifieur interne : 001021 ( Main/Exploration ); précédent : 001020; suivant : 001022

Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.

Auteurs : Lisa Jolly [Royaume-Uni] ; Anastasios Stavrou [Royaume-Uni] ; Gilles Vanderstoken [Canada] ; Victoria A. Meliopoulos [États-Unis] ; Anthony Habgood [Royaume-Uni] ; Amanda L. Tatler [Royaume-Uni] ; Joanne Porte [Royaume-Uni] ; Alan Knox [Royaume-Uni] ; Paul Weinreb [États-Unis] ; Shelia Violette [États-Unis] ; Tracy Hussell [Royaume-Uni] ; Martin Kolb [Canada] ; Martin R. Stampfli [Canada] ; Stacey Schultz-Cherry [États-Unis] ; Gisli Jenkins [Royaume-Uni]

Source :

The Journal of biological chemistry [ 1083-351X ] ; 2014.

RBID : pubmed:25339175

Descripteurs français

English descriptors

KwdEn :
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives), 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (pharmacology), Animals, Antigens, Neoplasm (genetics), Antigens, Neoplasm (metabolism), Antiviral Agents (pharmacology), Apoptosis, Cell Line, Transformed, Collagen (metabolism), Dogs, Epithelial Cells (drug effects), Epithelial Cells (metabolism), Epithelial Cells (virology), Host-Pathogen Interactions, Humans, Immunoblotting, Influenza A Virus, H1N1 Subtype (physiology), Integrins (genetics), Integrins (metabolism), Lung (metabolism), Lung (virology), Madin Darby Canine Kidney Cells, Mice, Inbred C57BL, Mice, Knockout, Orthomyxoviridae Infections (genetics), Orthomyxoviridae Infections (metabolism), Orthomyxoviridae Infections (virology), Phosphorylation (drug effects), Poly I-C (pharmacology), Smad3 Protein (genetics), Smad3 Protein (metabolism), Toll-Like Receptor 3 (metabolism), Transforming Growth Factor beta (genetics), Transforming Growth Factor beta (metabolism), rho-Associated Kinases (antagonists & inhibitors), rho-Associated Kinases (metabolism).
MESH :
- chemical , analogs & derivatives : 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine.
- chemical , antagonists & inhibitors : rho-Associated Kinases.
- chemical , genetics : Antigens, Neoplasm, Integrins, Smad3 Protein, Transforming Growth Factor beta.
- chemical , metabolism : Antigens, Neoplasm, Collagen, Integrins, Smad3 Protein, Toll-Like Receptor 3, Transforming Growth Factor beta, rho-Associated Kinases.
- chemical , pharmacology : 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Antiviral Agents, Poly I-C.
- drug effects : Epithelial Cells, Phosphorylation.
- genetics : Orthomyxoviridae Infections.
- metabolism : Epithelial Cells, Lung, Orthomyxoviridae Infections.
- physiology : Influenza A Virus, H1N1 Subtype.
- virology : Epithelial Cells, Lung, Orthomyxoviridae Infections.
- Animals, Apoptosis, Cell Line, Transformed, Dogs, Host-Pathogen Interactions, Humans, Immunoblotting, Madin Darby Canine Kidney Cells, Mice, Inbred C57BL, Mice, Knockout.

Abstract

Influenza infection exacerbates chronic pulmonary diseases, including idiopathic pulmonary fibrosis. A central pathway in the pathogenesis of idiopathic pulmonary fibrosis is epithelial injury leading to activation of transforming growth factor β (TGFβ). The mechanism and functional consequences of influenza-induced activation of epithelial TGFβ are unclear. Influenza stimulates toll-like receptor 3 (TLR3), which can increase RhoA activity, a key event prior to activation of TGFβ by the αvβ6 integrin. We hypothesized that influenza would stimulate TLR3 leading to activation of latent TGFβ via αvβ6 integrin in epithelial cells. Using H1152 (IC50 6.1 μm) to inhibit Rho kinase and 6.3G9 to inhibit αvβ6 integrins, we demonstrate their involvement in influenza (A/PR/8/34 H1N1) and poly(I:C)-induced TGFβ activation. We confirm the involvement of TLR3 in this process using chloroquine (IC50 11.9 μm) and a dominant negative TLR3 construct (pZERO-hTLR3). Examination of lungs from influenza-infected mice revealed augmented levels of collagen deposition, phosphorylated Smad2/3, αvβ6 integrin, and apoptotic cells. Finally, we demonstrate that αvβ6 integrin-mediated TGFβ activity following influenza infection promotes epithelial cell death in vitro and enhanced collagen deposition in vivo and that this response is diminished in Smad3 knock-out mice. These data show that H1N1 and poly(I:C) can induce αvβ6 integrin-dependent TGFβ activity in epithelial cells via stimulation of TLR3 and suggest a novel mechanism by which influenza infection may promote collagen deposition in fibrotic lung disease.

DOI: 10.1074/jbc.M114.582262
PubMed: 25339175

Affiliations:

Le document en format XML

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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Vanderstoken, Gilles" sort="Vanderstoken, Gilles" uniqKey="Vanderstoken G" first="Gilles" last="Vanderstoken">Gilles Vanderstoken</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
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<author><name sortKey="Habgood, Anthony" sort="Habgood, Anthony" uniqKey="Habgood A" first="Anthony" last="Habgood">Anthony Habgood</name>
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<author><name sortKey="Tatler, Amanda L" sort="Tatler, Amanda L" uniqKey="Tatler A" first="Amanda L" last="Tatler">Amanda L. Tatler</name>
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<author><name sortKey="Porte, Joanne" sort="Porte, Joanne" uniqKey="Porte J" first="Joanne" last="Porte">Joanne Porte</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
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<author><name sortKey="Knox, Alan" sort="Knox, Alan" uniqKey="Knox A" first="Alan" last="Knox">Alan Knox</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
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<placeName><settlement type="city">Nottingham</settlement>
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<region type="région" nuts="1">Nottinghamshire</region>
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<author><name sortKey="Weinreb, Paul" sort="Weinreb, Paul" uniqKey="Weinreb P" first="Paul" last="Weinreb">Paul Weinreb</name>
<affiliation wicri:level="2"><nlm:affiliation>Biogen Idec Inc., Cambridge, Massachusetts 02142.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
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<wicri:cityArea>Biogen Idec Inc., Cambridge</wicri:cityArea>
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<author><name sortKey="Violette, Shelia" sort="Violette, Shelia" uniqKey="Violette S" first="Shelia" last="Violette">Shelia Violette</name>
<affiliation wicri:level="2"><nlm:affiliation>Biogen Idec Inc., Cambridge, Massachusetts 02142.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Biogen Idec Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hussell, Tracy" sort="Hussell, Tracy" uniqKey="Hussell T" first="Tracy" last="Hussell">Tracy Hussell</name>
<affiliation wicri:level="4"><nlm:affiliation>the Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>the Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT</wicri:regionArea>
<orgName type="university">Université de Manchester</orgName>
<placeName><settlement type="city">Manchester</settlement>
<region type="nation">Angleterre</region>
<region nuts="2" type="region">Grand Manchester</region>
</placeName>
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<author><name sortKey="Kolb, Martin" sort="Kolb, Martin" uniqKey="Kolb M" first="Martin" last="Kolb">Martin Kolb</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stampfli, Martin R" sort="Stampfli, Martin R" uniqKey="Stampfli M" first="Martin R" last="Stampfli">Martin R. Stampfli</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schultz Cherry, Stacey" sort="Schultz Cherry, Stacey" uniqKey="Schultz Cherry S" first="Stacey" last="Schultz-Cherry">Stacey Schultz-Cherry</name>
<affiliation wicri:level="2"><nlm:affiliation>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jenkins, Gisli" sort="Jenkins, Gisli" uniqKey="Jenkins G" first="Gisli" last="Jenkins">Gisli Jenkins</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom, gisli.jenkins@nottingham.ac.uk.</nlm:affiliation>
<country wicri:rule="url">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.</title>
<author><name sortKey="Jolly, Lisa" sort="Jolly, Lisa" uniqKey="Jolly L" first="Lisa" last="Jolly">Lisa Jolly</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stavrou, Anastasios" sort="Stavrou, Anastasios" uniqKey="Stavrou A" first="Anastasios" last="Stavrou">Anastasios Stavrou</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vanderstoken, Gilles" sort="Vanderstoken, Gilles" uniqKey="Vanderstoken G" first="Gilles" last="Vanderstoken">Gilles Vanderstoken</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meliopoulos, Victoria A" sort="Meliopoulos, Victoria A" uniqKey="Meliopoulos V" first="Victoria A" last="Meliopoulos">Victoria A. Meliopoulos</name>
<affiliation wicri:level="2"><nlm:affiliation>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Habgood, Anthony" sort="Habgood, Anthony" uniqKey="Habgood A" first="Anthony" last="Habgood">Anthony Habgood</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tatler, Amanda L" sort="Tatler, Amanda L" uniqKey="Tatler A" first="Amanda L" last="Tatler">Amanda L. Tatler</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Porte, Joanne" sort="Porte, Joanne" uniqKey="Porte J" first="Joanne" last="Porte">Joanne Porte</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knox, Alan" sort="Knox, Alan" uniqKey="Knox A" first="Alan" last="Knox">Alan Knox</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weinreb, Paul" sort="Weinreb, Paul" uniqKey="Weinreb P" first="Paul" last="Weinreb">Paul Weinreb</name>
<affiliation wicri:level="2"><nlm:affiliation>Biogen Idec Inc., Cambridge, Massachusetts 02142.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Biogen Idec Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Violette, Shelia" sort="Violette, Shelia" uniqKey="Violette S" first="Shelia" last="Violette">Shelia Violette</name>
<affiliation wicri:level="2"><nlm:affiliation>Biogen Idec Inc., Cambridge, Massachusetts 02142.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Biogen Idec Inc., Cambridge</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hussell, Tracy" sort="Hussell, Tracy" uniqKey="Hussell T" first="Tracy" last="Hussell">Tracy Hussell</name>
<affiliation wicri:level="4"><nlm:affiliation>the Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>the Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT</wicri:regionArea>
<orgName type="university">Université de Manchester</orgName>
<placeName><settlement type="city">Manchester</settlement>
<region type="nation">Angleterre</region>
<region nuts="2" type="region">Grand Manchester</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kolb, Martin" sort="Kolb, Martin" uniqKey="Kolb M" first="Martin" last="Kolb">Martin Kolb</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stampfli, Martin R" sort="Stampfli, Martin R" uniqKey="Stampfli M" first="Martin R" last="Stampfli">Martin R. Stampfli</name>
<affiliation wicri:level="4"><nlm:affiliation>the McMaster Immunology Research Centre and Firestone Institute at St. Joseph's Health Care, McMaster University, Hamilton, Ontario L8S4L8, Canada, and.</nlm:affiliation>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schultz Cherry, Stacey" sort="Schultz Cherry, Stacey" uniqKey="Schultz Cherry S" first="Stacey" last="Schultz-Cherry">Stacey Schultz-Cherry</name>
<affiliation wicri:level="2"><nlm:affiliation>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jenkins, Gisli" sort="Jenkins, Gisli" uniqKey="Jenkins G" first="Gisli" last="Jenkins">Gisli Jenkins</name>
<affiliation wicri:level="4"><nlm:affiliation>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom, gisli.jenkins@nottingham.ac.uk.</nlm:affiliation>
<country wicri:rule="url">Royaume-Uni</country>
<wicri:regionArea>From the Nottingham Respiratory Research Unit, University of Nottingham, Nottingham University Hospitals, Clinical Sciences Building, City Hospital Campus, Nottingham NG5 1PB, United Kingdom</wicri:regionArea>
<orgName type="university">Université de Nottingham</orgName>
<placeName><settlement type="city">Nottingham</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Nottinghamshire</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of biological chemistry</title>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives)</term>
<term>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (pharmacology)</term>
<term>Animals</term>
<term>Antigens, Neoplasm (genetics)</term>
<term>Antigens, Neoplasm (metabolism)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Apoptosis</term>
<term>Cell Line, Transformed</term>
<term>Collagen (metabolism)</term>
<term>Dogs</term>
<term>Epithelial Cells (drug effects)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Epithelial Cells (virology)</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Immunoblotting</term>
<term>Influenza A Virus, H1N1 Subtype (physiology)</term>
<term>Integrins (genetics)</term>
<term>Integrins (metabolism)</term>
<term>Lung (metabolism)</term>
<term>Lung (virology)</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Orthomyxoviridae Infections (genetics)</term>
<term>Orthomyxoviridae Infections (metabolism)</term>
<term>Orthomyxoviridae Infections (virology)</term>
<term>Phosphorylation (drug effects)</term>
<term>Poly I-C (pharmacology)</term>
<term>Smad3 Protein (genetics)</term>
<term>Smad3 Protein (metabolism)</term>
<term>Toll-Like Receptor 3 (metabolism)</term>
<term>Transforming Growth Factor beta (genetics)</term>
<term>Transforming Growth Factor beta (metabolism)</term>
<term>rho-Associated Kinases (antagonists & inhibitors)</term>
<term>rho-Associated Kinases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>1-(5-Isoquinolylsulfonyl)-2-méthyl-pipérazine (analogues et dérivés)</term>
<term>1-(5-Isoquinolylsulfonyl)-2-méthyl-pipérazine (pharmacologie)</term>
<term>Animaux</term>
<term>Antigènes néoplasiques (génétique)</term>
<term>Antigènes néoplasiques (métabolisme)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Apoptose</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Cellules épithéliales ()</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Cellules épithéliales (virologie)</term>
<term>Chiens</term>
<term>Collagène (métabolisme)</term>
<term>Facteur de croissance transformant bêta (génétique)</term>
<term>Facteur de croissance transformant bêta (métabolisme)</term>
<term>Humains</term>
<term>Immunotransfert</term>
<term>Infections à Orthomyxoviridae (génétique)</term>
<term>Infections à Orthomyxoviridae (métabolisme)</term>
<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Interactions hôte-pathogène</term>
<term>Intégrines (génétique)</term>
<term>Intégrines (métabolisme)</term>
<term>Lignée de cellules transformées</term>
<term>Phosphorylation ()</term>
<term>Poly I-C (pharmacologie)</term>
<term>Poumon (métabolisme)</term>
<term>Poumon (virologie)</term>
<term>Protéine Smad-3 (génétique)</term>
<term>Protéine Smad-3 (métabolisme)</term>
<term>Récepteur de type Toll-3 (métabolisme)</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Sous-type H1N1 du virus de la grippe A (physiologie)</term>
<term>rho-Associated Kinases (antagonistes et inhibiteurs)</term>
<term>rho-Associated Kinases (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>rho-Associated Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Neoplasm</term>
<term>Integrins</term>
<term>Smad3 Protein</term>
<term>Transforming Growth Factor beta</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, Neoplasm</term>
<term>Collagen</term>
<term>Integrins</term>
<term>Smad3 Protein</term>
<term>Toll-Like Receptor 3</term>
<term>Transforming Growth Factor beta</term>
<term>rho-Associated Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine</term>
<term>Antiviral Agents</term>
<term>Poly I-C</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>1-(5-Isoquinolylsulfonyl)-2-méthyl-pipérazine</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>rho-Associated Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Epithelial Cells</term>
<term>Phosphorylation</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes néoplasiques</term>
<term>Facteur de croissance transformant bêta</term>
<term>Infections à Orthomyxoviridae</term>
<term>Intégrines</term>
<term>Protéine Smad-3</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Epithelial Cells</term>
<term>Lung</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes néoplasiques</term>
<term>Cellules épithéliales</term>
<term>Collagène</term>
<term>Facteur de croissance transformant bêta</term>
<term>Infections à Orthomyxoviridae</term>
<term>Intégrines</term>
<term>Poumon</term>
<term>Protéine Smad-3</term>
<term>Récepteur de type Toll-3</term>
<term>rho-Associated Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>1-(5-Isoquinolylsulfonyl)-2-méthyl-pipérazine</term>
<term>Antiviraux</term>
<term>Poly I-C</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules épithéliales</term>
<term>Infections à Orthomyxoviridae</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Epithelial Cells</term>
<term>Lung</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Apoptosis</term>
<term>Cell Line, Transformed</term>
<term>Dogs</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Immunoblotting</term>
<term>Madin Darby Canine Kidney Cells</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Apoptose</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Cellules épithéliales</term>
<term>Chiens</term>
<term>Humains</term>
<term>Immunotransfert</term>
<term>Interactions hôte-pathogène</term>
<term>Lignée de cellules transformées</term>
<term>Phosphorylation</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Influenza infection exacerbates chronic pulmonary diseases, including idiopathic pulmonary fibrosis. A central pathway in the pathogenesis of idiopathic pulmonary fibrosis is epithelial injury leading to activation of transforming growth factor β (TGFβ). The mechanism and functional consequences of influenza-induced activation of epithelial TGFβ are unclear. Influenza stimulates toll-like receptor 3 (TLR3), which can increase RhoA activity, a key event prior to activation of TGFβ by the αvβ6 integrin. We hypothesized that influenza would stimulate TLR3 leading to activation of latent TGFβ via αvβ6 integrin in epithelial cells. Using H1152 (IC50 6.1 μm) to inhibit Rho kinase and 6.3G9 to inhibit αvβ6 integrins, we demonstrate their involvement in influenza (A/PR/8/34 H1N1) and poly(I:C)-induced TGFβ activation. We confirm the involvement of TLR3 in this process using chloroquine (IC50 11.9 μm) and a dominant negative TLR3 construct (pZERO-hTLR3). Examination of lungs from influenza-infected mice revealed augmented levels of collagen deposition, phosphorylated Smad2/3, αvβ6 integrin, and apoptotic cells. Finally, we demonstrate that αvβ6 integrin-mediated TGFβ activity following influenza infection promotes epithelial cell death in vitro and enhanced collagen deposition in vivo and that this response is diminished in Smad3 knock-out mice. These data show that H1N1 and poly(I:C) can induce αvβ6 integrin-dependent TGFβ activity in epithelial cells via stimulation of TLR3 and suggest a novel mechanism by which influenza infection may promote collagen deposition in fibrotic lung disease. </div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Grand Manchester</li>
<li>Massachusetts</li>
<li>Nottinghamshire</li>
<li>Ontario</li>
<li>Tennessee</li>
</region>
<settlement><li>Hamilton (Ontario)</li>
<li>Manchester</li>
<li>Nottingham</li>
</settlement>
<orgName><li>Université McMaster</li>
<li>Université de Manchester</li>
<li>Université de Nottingham</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Jolly, Lisa" sort="Jolly, Lisa" uniqKey="Jolly L" first="Lisa" last="Jolly">Lisa Jolly</name>
</region>
<name sortKey="Habgood, Anthony" sort="Habgood, Anthony" uniqKey="Habgood A" first="Anthony" last="Habgood">Anthony Habgood</name>
<name sortKey="Hussell, Tracy" sort="Hussell, Tracy" uniqKey="Hussell T" first="Tracy" last="Hussell">Tracy Hussell</name>
<name sortKey="Jenkins, Gisli" sort="Jenkins, Gisli" uniqKey="Jenkins G" first="Gisli" last="Jenkins">Gisli Jenkins</name>
<name sortKey="Knox, Alan" sort="Knox, Alan" uniqKey="Knox A" first="Alan" last="Knox">Alan Knox</name>
<name sortKey="Porte, Joanne" sort="Porte, Joanne" uniqKey="Porte J" first="Joanne" last="Porte">Joanne Porte</name>
<name sortKey="Stavrou, Anastasios" sort="Stavrou, Anastasios" uniqKey="Stavrou A" first="Anastasios" last="Stavrou">Anastasios Stavrou</name>
<name sortKey="Tatler, Amanda L" sort="Tatler, Amanda L" uniqKey="Tatler A" first="Amanda L" last="Tatler">Amanda L. Tatler</name>
</country>
<country name="Canada"><region name="Ontario"><name sortKey="Vanderstoken, Gilles" sort="Vanderstoken, Gilles" uniqKey="Vanderstoken G" first="Gilles" last="Vanderstoken">Gilles Vanderstoken</name>
</region>
<name sortKey="Kolb, Martin" sort="Kolb, Martin" uniqKey="Kolb M" first="Martin" last="Kolb">Martin Kolb</name>
<name sortKey="Stampfli, Martin R" sort="Stampfli, Martin R" uniqKey="Stampfli M" first="Martin R" last="Stampfli">Martin R. Stampfli</name>
</country>
<country name="États-Unis"><region name="Tennessee"><name sortKey="Meliopoulos, Victoria A" sort="Meliopoulos, Victoria A" uniqKey="Meliopoulos V" first="Victoria A" last="Meliopoulos">Victoria A. Meliopoulos</name>
</region>
<name sortKey="Schultz Cherry, Stacey" sort="Schultz Cherry, Stacey" uniqKey="Schultz Cherry S" first="Stacey" last="Schultz-Cherry">Stacey Schultz-Cherry</name>
<name sortKey="Violette, Shelia" sort="Violette, Shelia" uniqKey="Violette S" first="Shelia" last="Violette">Shelia Violette</name>
<name sortKey="Weinreb, Paul" sort="Weinreb, Paul" uniqKey="Weinreb P" first="Paul" last="Weinreb">Paul Weinreb</name>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration Chloroquine

Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.

Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.

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