TocilizumabV1, Main, Exploration, bibRecord, 001739

Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.

Identifieur interne : 001739 ( Main/Exploration ); précédent : 001738; suivant : 001740

Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.

Auteurs : Neda Farahi [Royaume-Uni] ; Ellie Paige [Royaume-Uni] ; Jozef Balla [Royaume-Uni] ; Emily Prudence [Royaume-Uni] ; Ricardo C. Ferreira [Royaume-Uni] ; Mark Southwood [Royaume-Uni] ; Sarah L. Appleby [Royaume-Uni] ; Per Bakke [Norvège] ; Amund Gulsvik [Norvège] ; Augusto A. Litonjua [États-Unis] ; David Sparrow [États-Unis] ; Edwin K. Silverman [États-Unis] ; Michael H. Cho [États-Unis] ; John Danesh [Royaume-Uni] ; Dirk S. Paul [Royaume-Uni] ; Daniel F. Freitag [Royaume-Uni] ; Edwin R. Chilvers [Royaume-Uni]

Source :

Human molecular genetics [ 1460-2083 ] ; 2017.

RBID : pubmed:28334838

Descripteurs français

KwdFr :
- Asthme (anatomopathologie), Asthme (génétique), Asthme (sang), Broncho-pneumopathie chronique obstructive (anatomopathologie), Broncho-pneumopathie chronique obstructive (génétique), Broncho-pneumopathie chronique obstructive (sang), Femelle, Granulocytes neutrophiles (anatomopathologie), Granulocytes neutrophiles (métabolisme), Humains, Mâle, Poumon (anatomopathologie), Poumon (métabolisme), Récepteurs à l'interleukine-6 (génétique), Études d'associations génétiques.
MESH :
- anatomopathologie : Asthme, Broncho-pneumopathie chronique obstructive, Granulocytes neutrophiles, Poumon.
- génétique : Asthme, Broncho-pneumopathie chronique obstructive, Récepteurs à l'interleukine-6.
- métabolisme : Granulocytes neutrophiles, Poumon.
- sang : Asthme, Broncho-pneumopathie chronique obstructive.
- Femelle, Humains, Mâle, Études d'associations génétiques.

English descriptors

KwdEn :
- Asthma (blood), Asthma (genetics), Asthma (pathology), Female, Genetic Association Studies, Humans, Lung (metabolism), Lung (pathology), Male, Neutrophils (metabolism), Neutrophils (pathology), Pulmonary Disease, Chronic Obstructive (blood), Pulmonary Disease, Chronic Obstructive (genetics), Pulmonary Disease, Chronic Obstructive (pathology), Receptors, Interleukin-6 (genetics).
MESH :
- chemical , genetics : Receptors, Interleukin-6.
- blood : Asthma, Pulmonary Disease, Chronic Obstructive.
- genetics : Asthma, Pulmonary Disease, Chronic Obstructive.
- metabolism : Lung, Neutrophils.
- pathology : Asthma, Lung, Neutrophils, Pulmonary Disease, Chronic Obstructive.
- Female, Genetic Association Studies, Humans, Male.

Abstract

The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated. The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung. We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort. Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]). Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]). In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers. Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab. In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells. However, we were unable to identify evidence for an association between Asp358Ala and COPD.

DOI: 10.1093/hmg/ddx053
PubMed: 28334838

Affiliations:

Le document en format XML

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<author><name sortKey="Bakke, Per" sort="Bakke, Per" uniqKey="Bakke P" first="Per" last="Bakke">Per Bakke</name>
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<author><name sortKey="Gulsvik, Amund" sort="Gulsvik, Amund" uniqKey="Gulsvik A" first="Amund" last="Gulsvik">Amund Gulsvik</name>
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<author><name sortKey="Silverman, Edwin K" sort="Silverman, Edwin K" uniqKey="Silverman E" first="Edwin K" last="Silverman">Edwin K. Silverman</name>
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<author><name sortKey="Cho, Michael H" sort="Cho, Michael H" uniqKey="Cho M" first="Michael H" last="Cho">Michael H. Cho</name>
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<author><name sortKey="Paul, Dirk S" sort="Paul, Dirk S" uniqKey="Paul D" first="Dirk S" last="Paul">Dirk S. Paul</name>
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<author><name sortKey="Freitag, Daniel F" sort="Freitag, Daniel F" uniqKey="Freitag D" first="Daniel F" last="Freitag">Daniel F. Freitag</name>
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<author><name sortKey="Chilvers, Edwin R" sort="Chilvers, Edwin R" uniqKey="Chilvers E" first="Edwin R" last="Chilvers">Edwin R. Chilvers</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.</title>
<author><name sortKey="Farahi, Neda" sort="Farahi, Neda" uniqKey="Farahi N" first="Neda" last="Farahi">Neda Farahi</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Paige, Ellie" sort="Paige, Ellie" uniqKey="Paige E" first="Ellie" last="Paige">Ellie Paige</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Balla, Jozef" sort="Balla, Jozef" uniqKey="Balla J" first="Jozef" last="Balla">Jozef Balla</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Prudence, Emily" sort="Prudence, Emily" uniqKey="Prudence E" first="Emily" last="Prudence">Emily Prudence</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ</wicri:regionArea>
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<author><name sortKey="Ferreira, Ricardo C" sort="Ferreira, Ricardo C" uniqKey="Ferreira R" first="Ricardo C" last="Ferreira">Ricardo C. Ferreira</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Nuffield Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN</wicri:regionArea>
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<author><name sortKey="Southwood, Mark" sort="Southwood, Mark" uniqKey="Southwood M" first="Mark" last="Southwood">Mark Southwood</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ</wicri:regionArea>
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<author><name sortKey="Appleby, Sarah L" sort="Appleby, Sarah L" uniqKey="Appleby S" first="Sarah L" last="Appleby">Sarah L. Appleby</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ</wicri:regionArea>
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<author><name sortKey="Bakke, Per" sort="Bakke, Per" uniqKey="Bakke P" first="Per" last="Bakke">Per Bakke</name>
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<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Clinical Science, University of Bergen, Bergen 5021</wicri:regionArea>
<wicri:noRegion>Bergen 5021</wicri:noRegion>
</affiliation>
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<author><name sortKey="Gulsvik, Amund" sort="Gulsvik, Amund" uniqKey="Gulsvik A" first="Amund" last="Gulsvik">Amund Gulsvik</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Science, University of Bergen, Bergen 5021, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Clinical Science, University of Bergen, Bergen 5021</wicri:regionArea>
<wicri:noRegion>Bergen 5021</wicri:noRegion>
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<author><name sortKey="Litonjua, Augusto A" sort="Litonjua, Augusto A" uniqKey="Litonjua A" first="Augusto A" last="Litonjua">Augusto A. Litonjua</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Brigham and Women's Hospital and Harvard Medical School, Boston 02115, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
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<author><name sortKey="Sparrow, David" sort="Sparrow, David" uniqKey="Sparrow D" first="David" last="Sparrow">David Sparrow</name>
<affiliation wicri:level="2"><nlm:affiliation>VA Boston Healthcare System and School of Medicine, Boston University, Boston 02132, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>VA Boston Healthcare System and School of Medicine, Boston University, Boston 02132, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
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<author><name sortKey="Silverman, Edwin K" sort="Silverman, Edwin K" uniqKey="Silverman E" first="Edwin K" last="Silverman">Edwin K. Silverman</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Brigham and Women's Hospital and Harvard Medical School, Boston 02115, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
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<author><name sortKey="Cho, Michael H" sort="Cho, Michael H" uniqKey="Cho M" first="Michael H" last="Cho">Michael H. Cho</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Brigham and Women's Hospital and Harvard Medical School, Boston 02115, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
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<author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Paul, Dirk S" sort="Paul, Dirk S" uniqKey="Paul D" first="Dirk S" last="Paul">Dirk S. Paul</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Freitag, Daniel F" sort="Freitag, Daniel F" uniqKey="Freitag D" first="Daniel F" last="Freitag">Daniel F. Freitag</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge CB1 8RN, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chilvers, Edwin R" sort="Chilvers, Edwin R" uniqKey="Chilvers E" first="Edwin R" last="Chilvers">Edwin R. Chilvers</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ</wicri:regionArea>
<wicri:noRegion>Cambridge CB2 0QQ</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Human molecular genetics</title>
<idno type="eISSN">1460-2083</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Asthma (blood)</term>
<term>Asthma (genetics)</term>
<term>Asthma (pathology)</term>
<term>Female</term>
<term>Genetic Association Studies</term>
<term>Humans</term>
<term>Lung (metabolism)</term>
<term>Lung (pathology)</term>
<term>Male</term>
<term>Neutrophils (metabolism)</term>
<term>Neutrophils (pathology)</term>
<term>Pulmonary Disease, Chronic Obstructive (blood)</term>
<term>Pulmonary Disease, Chronic Obstructive (genetics)</term>
<term>Pulmonary Disease, Chronic Obstructive (pathology)</term>
<term>Receptors, Interleukin-6 (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Asthme (anatomopathologie)</term>
<term>Asthme (génétique)</term>
<term>Asthme (sang)</term>
<term>Broncho-pneumopathie chronique obstructive (anatomopathologie)</term>
<term>Broncho-pneumopathie chronique obstructive (génétique)</term>
<term>Broncho-pneumopathie chronique obstructive (sang)</term>
<term>Femelle</term>
<term>Granulocytes neutrophiles (anatomopathologie)</term>
<term>Granulocytes neutrophiles (métabolisme)</term>
<term>Humains</term>
<term>Mâle</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (métabolisme)</term>
<term>Récepteurs à l'interleukine-6 (génétique)</term>
<term>Études d'associations génétiques</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Interleukin-6</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Asthme</term>
<term>Broncho-pneumopathie chronique obstructive</term>
<term>Granulocytes neutrophiles</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Asthma</term>
<term>Pulmonary Disease, Chronic Obstructive</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Asthma</term>
<term>Pulmonary Disease, Chronic Obstructive</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Asthme</term>
<term>Broncho-pneumopathie chronique obstructive</term>
<term>Récepteurs à l'interleukine-6</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term>
<term>Neutrophils</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Granulocytes neutrophiles</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Asthma</term>
<term>Lung</term>
<term>Neutrophils</term>
<term>Pulmonary Disease, Chronic Obstructive</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Asthme</term>
<term>Broncho-pneumopathie chronique obstructive</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Female</term>
<term>Genetic Association Studies</term>
<term>Humans</term>
<term>Male</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Études d'associations génétiques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated. The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung. We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort. Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]). Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]). In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers. Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab. In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells. However, we were unable to identify evidence for an association between Asp358Ala and COPD.</div>
</front>
</TEI>
<affiliations><list><country><li>Norvège</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Massachusetts</li>
<li>Oxfordshire</li>
</region>
<settlement><li>Oxford</li>
</settlement>
<orgName><li>Université d'Oxford</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Farahi, Neda" sort="Farahi, Neda" uniqKey="Farahi N" first="Neda" last="Farahi">Neda Farahi</name>
</noRegion>
<name sortKey="Appleby, Sarah L" sort="Appleby, Sarah L" uniqKey="Appleby S" first="Sarah L" last="Appleby">Sarah L. Appleby</name>
<name sortKey="Balla, Jozef" sort="Balla, Jozef" uniqKey="Balla J" first="Jozef" last="Balla">Jozef Balla</name>
<name sortKey="Chilvers, Edwin R" sort="Chilvers, Edwin R" uniqKey="Chilvers E" first="Edwin R" last="Chilvers">Edwin R. Chilvers</name>
<name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name>
<name sortKey="Ferreira, Ricardo C" sort="Ferreira, Ricardo C" uniqKey="Ferreira R" first="Ricardo C" last="Ferreira">Ricardo C. Ferreira</name>
<name sortKey="Freitag, Daniel F" sort="Freitag, Daniel F" uniqKey="Freitag D" first="Daniel F" last="Freitag">Daniel F. Freitag</name>
<name sortKey="Paige, Ellie" sort="Paige, Ellie" uniqKey="Paige E" first="Ellie" last="Paige">Ellie Paige</name>
<name sortKey="Paul, Dirk S" sort="Paul, Dirk S" uniqKey="Paul D" first="Dirk S" last="Paul">Dirk S. Paul</name>
<name sortKey="Prudence, Emily" sort="Prudence, Emily" uniqKey="Prudence E" first="Emily" last="Prudence">Emily Prudence</name>
<name sortKey="Southwood, Mark" sort="Southwood, Mark" uniqKey="Southwood M" first="Mark" last="Southwood">Mark Southwood</name>
</country>
<country name="Norvège"><noRegion><name sortKey="Bakke, Per" sort="Bakke, Per" uniqKey="Bakke P" first="Per" last="Bakke">Per Bakke</name>
</noRegion>
<name sortKey="Gulsvik, Amund" sort="Gulsvik, Amund" uniqKey="Gulsvik A" first="Amund" last="Gulsvik">Amund Gulsvik</name>
</country>
<country name="États-Unis"><region name="Massachusetts"><name sortKey="Litonjua, Augusto A" sort="Litonjua, Augusto A" uniqKey="Litonjua A" first="Augusto A" last="Litonjua">Augusto A. Litonjua</name>
</region>
<name sortKey="Cho, Michael H" sort="Cho, Michael H" uniqKey="Cho M" first="Michael H" last="Cho">Michael H. Cho</name>
<name sortKey="Silverman, Edwin K" sort="Silverman, Edwin K" uniqKey="Silverman E" first="Edwin K" last="Silverman">Edwin K. Silverman</name>
<name sortKey="Sparrow, David" sort="Sparrow, David" uniqKey="Sparrow D" first="David" last="Sparrow">David Sparrow</name>
</country>
</tree>
</affiliations>
</record>

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Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.

Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.

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