title: Regulation and function of epithelial secreted phospholipase A2 group X in asthma.
abstract: BACKGROUND
  Indirect airway hyperresponsiveness (AHR) is a fundamental feature of asthma that is manifest as exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 group X (sPLA2-X) plays a key role in regulating eicosanoid formation and the development of inflammation and AHR in murine models.
  
  
  OBJECTIVE
  We sought to examine sPLA2-X in the airway epithelium and airway wall of patients with asthma, the relationship to AHR in humans, and the regulation and function of sPLA2-X within the epithelium.
  
  
  METHODS
  We precisely phenotyped 34 patients with asthma (19 with and 15 without EIB) and 10 normal control subjects to examine in vivo differences in epithelial gene expression, quantitative morphometry of endobronchial biopsies, and levels of secreted protein. The regulation of sPLA2-X gene (PLA2G10) expression was examined in primary airway epithelial cell cultures. The function of epithelial sPLA2-X in eicosanoid formation was examined using PLA2 inhibitors and murine tracheal epithelial cells with Pla2g10 deletion.
  
  
  RESULTS
  We found that sPLA2-X protein is increased in the airways of patients with asthma and that epithelial-derived sPLA2-X may be increased in association with indirect AHR. The expression of sPLA2-X increases during in vitro epithelial differentiation; is regulated by inflammatory signals including tumor necrosis factor, IL-13, and IL-17; and is both secreted from the epithelium and directly participates in the release of arachidonic acid by epithelial cells.
  
  
  CONCLUSIONS
  These data reveal a relationship between epithelial-derived sPLA2-X and indirect AHR in asthma and that sPLA2-X serves as an epithelial regulator of inflammatory eicosanoid formation. Therapies targeting epithelial sPLA2-X may be useful in asthma.
authors.affiliation: Department of Medicine, University ofWashington, Seattle, WA, USA. tealh@u.washington.edu
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
authors.forename: Ying
authors.initials: Y
authors.lastname: Lai
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.forename: Cara L
authors.initials: CL
authors.lastname: Appel
authors.forename: Brian
authors.initials: B
authors.lastname: Johnson
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudkins
authors.forename: James G
authors.initials: JG
authors.lastname: Bollinger
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Hyde
authors.forename: William R
authors.initials: WR
authors.lastname: Henderson
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D001250:Asthma, Exercise-Induced / Q000235:genetics / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D054509:Group X Phospholipases A2 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D054509:Group X Phospholipases A2