Characterisation of eppin function: expression and activity in the lung

Aaron Scott, Arlene Glasgow, Donna Small, Simon Carlile, Maeliosa McCrudden, Denise McLean, Ryan Brown, Declan Doherty, Fionnuala Lundy, Umar Hamid, Cecilia O'Kane, Danny McAuley, Malcolm Brodlie, Michael Tunney, Joseph Elborn, Christopher Irwin, David Timson, Clifford Taggart, Sinead Weldon

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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 LPSinduced 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 immune response in the lung.
Original languageEnglish
Article number1601937
JournalEuropean Respiratory Journal
Volume50
Issue number1
DOIs
Publication statusPublished - 13 Jul 2017

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