A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation of the inflammatory response in the lung

Arlene M A Glasgow, Donna M Small, Aaron Scott, Denise T McLean, Nicolas Camper, Umar Hamid, Shauna Hegarty, Dhruv Parekh, Cecilia O'Kane, Fionnuala T Lundy, Paul McNally, J Stuart Elborn, Danny F McAuley, Sinéad Weldon*, Clifford C Taggart

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
183 Downloads (Pure)

Abstract

Introduction: Secretory leucocyte protease inhibitor and elafin are members of the whey acidic protein (WAP), or WAP four disulfide-core (WFDC), family of proteins and have multiple contributions to innate defence including inhibition of neutrophil serine proteases and inhibition of the inflammatory response to lipopolysaccharide (LPS). This study aimed to explore potential activities of WFDC12, a previously uncharacterised WFDC protein expressed in the lung. Methods: Recombinant expression and purification of WFDC12 were optimised in Escherichia coli. Antiprotease, antibacterial and immunomodulatory activities of recombinant WFDC12 were evaluated and levels of endogenous WFDC12 protein were characterised by immunostaining and ELISA. Results: Recombinant WFDC12 inhibited cathepsin G, but not elastase or proteinase-3 activity. Monocytic cells pretreated with recombinant WFDC12 before LPS stimulation produced significantly lower levels of the pro-inflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared with cells stimulated with LPS alone. Recombinant WFDC12 became conjugated to fibronectin in a transglutaminase-mediated reaction and retained antiprotease activity. In vivo WFDC12 expression was confirmed by immunostaining of human lung tissue sections. WFDC12 levels in human bronchoalveolar lavage fluid from healthy and lung-injured patients were quantitatively compared, showing WFDC12 to be elevated in both patients with acute respiratory distress syndrome and healthy subjects treated with LPS, relative to healthy controls. Conclusions: Together, these results suggest a role for this lesser known WFDC protein in the regulation of lung inflammation.

Original languageEnglish
Pages (from-to)426-32
JournalThorax
Volume70
Issue number5
Early online date13 Mar 2015
DOIs
Publication statusPublished - May 2015

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