title: A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation of the inflammatory response in the lung.
abstract: BACKGROUND
  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.
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Arlene M A
authors.initials: AM
authors.lastname: Glasgow
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Small
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Scott
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Denise T
authors.initials: DT
authors.lastname: McLean
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Camper
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Umar
authors.initials: U
authors.lastname: Hamid
authors.affiliation: Department of Pathology, Royal Victoria Hospital, Belfast, UK.
authors.forename: Shauna
authors.initials: S
authors.lastname: Hegarty
authors.affiliation: College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Parekh
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Cecilia
authors.initials: C
authors.lastname: O'Kane
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Fionnuala T
authors.initials: FT
authors.lastname: Lundy
authors.affiliation: Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: McNally
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Danny F
authors.initials: DF
authors.lastname: McAuley
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Sinéad
authors.initials: S
authors.lastname: Weldon
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK.
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Taggart
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects*; D046509:Tissue Culture Techniques
chemical_list: D008070:Lipopolysaccharides; D011506:Proteins; D011994:Recombinant Proteins; C447606:WFDC12 protein, human; D012697:Serine Endopeptidases
keywords: ARDS; Innate Immunity