Characterisation of eppin function: expression and activity in the lung

Research output: Contribution to journalArticle

Authors

  • Arlene Glasgow
  • Donna Small
  • Simon Carlile
  • Maelíosa McCrudden
  • Denise 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 J. Timson
  • Clifford C. Taggart
  • Sinéad Weldon

Colleges, School and Institutes

External organisations

  • Airway Innate Immunity Research Group, Centre for Experimental Medicine, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast
  • Centre for Experimental Medicine, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast
  • Paediatric Respiratory Unit, Great North Children's Hospital and Institute of Cellular Medicine, Newcastle University
  • Halo, School of Pharmacy, Queen's University Belfast
  • Centre for Dentistry, Queen's University Belfast
  • University of Brighton

Abstract

Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.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 Toll-like receptor agonists, cytokines and hormone receptor agonists. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor. Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide-induced chemokine production. Furthermore, eppin inhibited lipopolysaccharide-induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In anin vivomodel of lung inflammation induced by lipopolysaccharide, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine macrophage inflammatory protein-2.Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immune response in the lung.

Details

Original languageEnglish
JournalThe European respiratory journal
Volume50
Issue number1
Publication statusPublished - 31 Jul 2017