Characterisation of eppin function: expression and activity in the lung

Aaron Scott, Arlene Glasgow, Donna Small, Simon Carlile, Maelíosa T.C. McCrudden, Denise T.F. McLean, Ryan Brown, Declan Doherty, Fionnuala T. Lundy, Umar I. Hamid, Cecilia M. O'Kane, Daniel F. McAuley, Malcolm Brodlie, Michael Tunney, J. Stuart Elborn, Chris R. Irwin, David Timson, Clifford C. Taggart, Sinéad Weldon

Research output: Contribution to journalArticle

Abstract

Eppin is a serine protease inhibitor expressed in male reproductive tissues. In this study we have demonstrated novel sites of eppin expression in myeloid and epithelial cell lines with further confirmation in primary myeloid cell types. Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with Acute Respiratory Distress Syndrome and Cystic Fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with TLR agonists, cytokine stimulation and hormone receptor agonist stimulation. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor (EGF). Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide (LPS)-induced chemokine production. Furthermore, eppin inhibited LPS- induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by LPS, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine MIP-2. Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immuneresponse in the lung.
Original languageEnglish
JournalEuropean Respiratory Journal
Volume50
Issue number1
DOIs
Publication statusPublished - 13 Jul 2017

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Lipopolysaccharides
Myeloid Cells
Lung
Chemokine CXCL2
Serine Proteinase Inhibitors
Neutrophil Infiltration
Adult Respiratory Distress Syndrome
Chemokines
Epidermal Growth Factor
Cystic Fibrosis
Lung Diseases
Monocytes
Pneumonia
Neutrophils
Western Blotting
Epithelial Cells
Immunohistochemistry
Hormones
Cytokines
Cell Line

Bibliographical note

This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.

Cite this

Scott, A., Glasgow, A., Small, D., Carlile, S., McCrudden, M. T. C., McLean, D. T. F., ... Weldon, S. (2017). Characterisation of eppin function: expression and activity in the lung. European Respiratory Journal, 50(1). https://doi.org/10.1183/13993003.01937-2016
Scott, Aaron ; Glasgow, Arlene ; Small, Donna ; Carlile, Simon ; McCrudden, Maelíosa T.C. ; McLean, Denise T.F. ; Brown, Ryan ; Doherty, Declan ; Lundy, Fionnuala T. ; Hamid, Umar I. ; O'Kane, Cecilia M. ; McAuley, Daniel F. ; Brodlie, Malcolm ; Tunney, Michael ; Elborn, J. Stuart ; Irwin, Chris R. ; Timson, David ; Taggart, Clifford C. ; Weldon, Sinéad. / Characterisation of eppin function: expression and activity in the lung. In: European Respiratory Journal. 2017 ; Vol. 50, No. 1.
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abstract = "Eppin is a serine protease inhibitor expressed in male reproductive tissues. In this study we have demonstrated novel sites of eppin expression in myeloid and epithelial cell lines with further confirmation in primary myeloid cell types. Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with Acute Respiratory Distress Syndrome and Cystic Fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with TLR agonists, cytokine stimulation and hormone receptor agonist stimulation. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor (EGF). Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide (LPS)-induced chemokine production. Furthermore, eppin inhibited LPS- induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by LPS, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine MIP-2. Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immuneresponse in the lung.",
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Scott, A, Glasgow, A, Small, D, Carlile, S, McCrudden, MTC, McLean, DTF, Brown, R, Doherty, D, Lundy, FT, Hamid, UI, O'Kane, CM, McAuley, DF, Brodlie, M, Tunney, M, Elborn, JS, Irwin, CR, Timson, D, Taggart, CC & Weldon, S 2017, 'Characterisation of eppin function: expression and activity in the lung', European Respiratory Journal, vol. 50, no. 1. https://doi.org/10.1183/13993003.01937-2016

Characterisation of eppin function: expression and activity in the lung. / Scott, Aaron; Glasgow, Arlene; Small, Donna; Carlile, Simon; McCrudden, Maelíosa T.C.; McLean, Denise T.F.; Brown, Ryan; Doherty, Declan; Lundy, Fionnuala T.; Hamid, Umar I.; O'Kane, Cecilia M.; McAuley, Daniel F.; Brodlie, Malcolm; Tunney, Michael; Elborn, J. Stuart; Irwin, Chris R.; Timson, David; Taggart, Clifford C.; Weldon, Sinéad.

In: European Respiratory Journal, Vol. 50, No. 1, 13.07.2017.

Research output: Contribution to journalArticle

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AU - Scott, Aaron

AU - Glasgow, Arlene

AU - Small, Donna

AU - Carlile, Simon

AU - McCrudden, Maelíosa T.C.

AU - McLean, Denise T.F.

AU - Brown, Ryan

AU - Doherty, Declan

AU - Lundy, Fionnuala T.

AU - Hamid, Umar I.

AU - O'Kane, Cecilia M.

AU - McAuley, Daniel F.

AU - Brodlie, Malcolm

AU - Tunney, Michael

AU - Elborn, J. Stuart

AU - Irwin, Chris R.

AU - Timson, David

AU - Taggart, Clifford C.

AU - Weldon, Sinéad

N1 - This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.

PY - 2017/7/13

Y1 - 2017/7/13

N2 - Eppin is a serine protease inhibitor expressed in male reproductive tissues. In this study we have demonstrated novel sites of eppin expression in myeloid and epithelial cell lines with further confirmation in primary myeloid cell types. Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with Acute Respiratory Distress Syndrome and Cystic Fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with TLR agonists, cytokine stimulation and hormone receptor agonist stimulation. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor (EGF). Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide (LPS)-induced chemokine production. Furthermore, eppin inhibited LPS- induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by LPS, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine MIP-2. Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immuneresponse in the lung.

AB - Eppin is a serine protease inhibitor expressed in male reproductive tissues. In this study we have demonstrated novel sites of eppin expression in myeloid and epithelial cell lines with further confirmation in primary myeloid cell types. Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with Acute Respiratory Distress Syndrome and Cystic Fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with TLR agonists, cytokine stimulation and hormone receptor agonist stimulation. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor (EGF). Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide (LPS)-induced chemokine production. Furthermore, eppin inhibited LPS- induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by LPS, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine MIP-2. Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immuneresponse in the lung.

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DO - 10.1183/13993003.01937-2016

M3 - Article

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JO - European Respiratory Journal

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SN - 0903-1936

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Scott A, Glasgow A, Small D, Carlile S, McCrudden MTC, McLean DTF et al. Characterisation of eppin function: expression and activity in the lung. European Respiratory Journal. 2017 Jul 13;50(1). https://doi.org/10.1183/13993003.01937-2016