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

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

doi:10.1093/hmg/ddx053

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

Neda Farahi, Ellie Paige, Jozef Balla, Emily Prudence, Ricardo C. Ferreira, Mark Southwood, Sarah L. Appleby, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Edwin K. Silverman, Michael H. Cho, John Danesh, Dirk S. Paul, Daniel F. Freitag^*, Edwin R. Chilvers

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

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 proinflammatory 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.

Original language	English
Article number	ddx053
Pages (from-to)	1584-1596
Number of pages	13
Journal	Human Molecular Genetics
Volume	26
Issue number	8
DOIs	https://doi.org/10.1093/hmg/ddx053
Publication status	Published - 15 Apr 2017
Externally published	Yes

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Farahi, N., Paige, E., Balla, J., Prudence, E., Ferreira, R. C., Southwood, M., Appleby, S. L., Bakke, P., Gulsvik, A., Litonjua, A. A., Sparrow, D., Silverman, E. K., Cho, M. H., Danesh, J., Paul, D. S., Freitag, D. F., & Chilvers, E. R. (2017). Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma. Human Molecular Genetics, 26(8), 1584-1596. Article ddx053. https://doi.org/10.1093/hmg/ddx053

@article{a3473f8a33e649d480d7afa0c766062d,

title = "Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma",

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 proinflammatory 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.",

author = "Neda Farahi and Ellie Paige and Jozef Balla and Emily Prudence and Ferreira, {Ricardo C.} and Mark Southwood and Appleby, {Sarah L.} and Per Bakke and Amund Gulsvik and Litonjua, {Augusto A.} and David Sparrow and Silverman, {Edwin K.} and Cho, {Michael H.} and John Danesh and Paul, {Dirk S.} and Freitag, {Daniel F.} and Chilvers, {Edwin R.}",

year = "2017",

month = apr,

day = "15",

doi = "10.1093/hmg/ddx053",

language = "English",

volume = "26",

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journal = "Human Molecular Genetics",

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Farahi, N, Paige, E, Balla, J, Prudence, E, Ferreira, RC, Southwood, M, Appleby, SL, Bakke, P, Gulsvik, A, Litonjua, AA, Sparrow, D, Silverman, EK, Cho, MH, Danesh, J, Paul, DS, Freitag, DF & Chilvers, ER 2017, 'Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma', Human Molecular Genetics, vol. 26, no. 8, ddx053, pp. 1584-1596. https://doi.org/10.1093/hmg/ddx053

TY - JOUR

T1 - Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma

AU - Farahi, Neda

AU - Paige, Ellie

AU - Balla, Jozef

AU - Prudence, Emily

AU - Ferreira, Ricardo C.

AU - Southwood, Mark

AU - Appleby, Sarah L.

AU - Bakke, Per

AU - Gulsvik, Amund

AU - Litonjua, Augusto A.

AU - Sparrow, David

AU - Silverman, Edwin K.

AU - Cho, Michael H.

AU - Danesh, John

AU - Paul, Dirk S.

AU - Freitag, Daniel F.

AU - Chilvers, Edwin R.

PY - 2017/4/15

Y1 - 2017/4/15

N2 - 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 proinflammatory 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.

AB - 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 proinflammatory 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.

UR - http://www.scopus.com/inward/record.url?scp=85019144153&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddx053

DO - 10.1093/hmg/ddx053

M3 - Article

SN - 0964-6906

VL - 26

SP - 1584

EP - 1596

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 8

M1 - ddx053

ER -

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

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